(and dosage form):
Each capsule contains alpha-methyldopa equivalent to anhydrous methyldopa 250 mg.
A7.1.3 Other hypotensives
Following oral administration, alpha-methyldopa causes progressive reductions in blood pressure and heart rate and are maximal at 4 to 6 hours and persist for as long as 24 hours after a single oral dose. The fall in blood pressure is greater in hypertensive than in normotensive subjects, and has variously been reported to be due to a decrease in cardiac output, peripheral resistance, or both. Alpha-methyldopa decreases plasma renin activity but it tends to cause sodium and water retention. Changes in fluid volumes could contribute to differences in cardiac output. It is also possible that changes observed during chronic administration represent predominantly, adaptations of the body to the primary effects of the drug. In general peripheral resistance and pressor reflexes tend to be more, and heart rate less decreased after chronic than after acute administration. Present evidence suggests that the antihypertensive effect of alpha-methyldopa is mainly due to an action on the C.N.S. Functional competence of sympathetic nerves during acute hypotensive effects of alpha-methyldopa is indicated by normal responses to nerve stimulation and to most cardiovascular reflexes in both laboratory animals and man. Responses to the Valsalva manoeuvre and cold pressor test have been reported inhibited after more prolonged alpha-methyldopa administration. Blood pressure after alpha-methyldopa is lower in the upright than in the supine position. The reduction of blood pressure induced by alpha-methyldopa has not been shown to involve any major changes in blood flow distribution. Renal blood flow and glomerular filtration are maintained or increased in hypertensive patients with both normal and reduced renal function.
Alpha-methyldopa is contra-indicated in persons known to be sensitive to it. It should be used with caution in patients with impaired kidney or liver function or with a history of liver disease or depression. It should not be given to patients with acute liver disease or phaeochromocytoma and should not be given during pregnancy.
DOSAGE AND DIRECTIONS FOR USE:
One capsule 2 or 3 times daily during the first 48 hours. Thereafter, the daily dosage may be adjusted preferably at intervals of not less than 48 hours, until an adequate response has been achieved. The usual dose is 0,5 g to 2 g daily. A suggested initial dose for children is 10 mg per kg body mass in divided doses.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Treatment with alpha-methyldopa is generally associated with a fairly high incidence of side-effects, usually mild but occasionally severe.
1. The most frequently occurring side effects are drowsiness, and other manifestations of central nervous system depression especially in the presence of renal failure. Changes in mental acuity with a decrease in concentration may result in mistakes with professional activities and an impaired capacity to drive motor vehicles. Existing depression may be aggravated and Normopress is best avoided in patients with a previous history of depression.
2. Unwanted hypotension appears to be more common in patients with renal impairment and in the elderly. Occasionally the hypotensive response to alpha-methyldopa has been life-threatening.
3. Alpha-methyldopa induced hepatotoxicity is well documented with a clinical picture of hepatitis with a fairly acute onset of symptoms; there is hepatocellular damage and sometimes cholestasis. Rarely, there may be massive liver cell necrosis with a fatal outcome especially after renewed exposure following previously demonstrated liver toxicity to the drug. In most cases, the hepatitis resolves after discontinuation of the drug, but the clinical picture of chronic active hepatitis has been seen.
4. Drug fever associated with symptoms resembling a general infectious disease has been described in about 3% of cases treated. The fever reaction is seen in the first few weeks of treatment. It is not clear whether continuation of administration predisposes the patient to other complications.
5. Immunological abnormalities are well recognised complications of long-term therapy with alpha-methyldopa viz. Coombs positive immunoglobulin test, and occasionally anaemia with prolonged usage. Development of a positive serum antinuclear factor; rheumatoid factor; and elevation of immunoglobulin A, immunoglobulin G and immunoglobulin M levels have been described.
6. Cases of skin disorders developing during (alpha-methyldopa) treatment and clearing after discontinuation of the drug have been reported.
7. Impairment of sexual function in men, with decrease in libido and failure of ejaculation, is common.
8. The following adverse reactions have been reported: paradoxical hypertensive reactions to intravenous administration, granulocytopenia and thrombocytopenia; Parkinsonism; non-puerperal lactation; increased serum prolactin levels, especially in doses of 1 g and upwards; malabsorption with Crohn's type granuloma, reversible on stopping in the drug; and several deaths, said to be due to hypersensitivity myocarditis, have been recorded.
9. Unwanted interactions between alpha-methyldopa and other drugs such as diuretic agents, beta-blockers and other antihypertensive agents and antidepressant drugs appear to occur. Severe hypotension may occur during anaesthesia in patients being treated with alpha-methyldopa. The combination of alpha-methyldopa with other potentially hepatotoxic agents, particularly halothane, is not advisable.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Excessive hypotension with bradycardia.
Symptomatic treatment is indicated.
CONDITIONS OF REGISTRATION:
Advertising to the professions only.
Blue and black imprinted capsules.
30, 100 and 500 capsules in polyethylene containers.
Keep container tightly closed.
Protect from light and moisture.
Store below 25°C.
Keep out of reach of children.
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
GEO SCHWULST LABS. LIMITED
1 Manchester Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
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