HYPOJIT 125
-
Chemical Name:
Methyldopa -
Therapeutic Category:
Cardiovascular drugs -
Pharmacologic Category:
Alpha2-Adrenergic Agonist -
Pharmaceutical Form:
Tablets -
Composition:
Methyldopa 125mg
HYPOJIT
Film Coated Tablets
Anhydrous Methyldopa
1-COMPOSITION:
HYPOJIT 125 - Film Coated Tablets: Each film coated tablet contains Methyldopa 125 mg.
HYPOJIT 250 - Film Coated Tablets: Each film coated tablet contains Methyldopa 250 mg.
Excipients:
Microcrystalline Cellulose, PVP-K/30, Aerosil, Citric Acid, Magnesium Stearate, Talc, Crosspovidone, HPMC, Titanium Dioxide, Quinoline yellow, Alcohol (97%), Triacetine.
2-MECHANISM of ACTION:
The antihypertensive effect of methyldopa is probably due to its metabolism to alpha-methyl noradrenaline, 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, adrenaline and noradrenaline.
3-PHARMACOKINETICS:
Absorption of oral methyldopa is variable and incomplete. Bioavailability after oral administration averages 25%. Peak concentrations in plasma occur at two to three hours. Plasma half-life is 1.8 ± 0.2 hours. Renal excretion accounts for about two thirds of drug clearance from plasma.
4-INDICATIONS:
It is indicated for the treatment of hypertension.
5-CONTRAINDICATIONS:
- In patients with Active hepatic disease, such as acute hepatitis and active cirrhosis
- In patients with Hypersensitivity (including hepatic disorders associated with previous methyldopa therapy) to any component of these products.
- In patients with Depression.
- In patients on therapy with monoamine oxidase inhibitors (MAOIs).
- It is not recommended for the treatment of phaeochromocytoma or paraganglioma.
- In patients with porphyria.
6-WARNINGS & PRECAUTIONS:
- Acquired haemolytic anaemia has occurred rarely. If anaemia is confirmed, tests should be done for haemolysis. If haemolytic anaemia is present, methyldopa should be discontinued.
- Some patients on continued therapy with methyldopa develop a positive Coombs test.
- 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. 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.
- 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.
7-EFFECTS On ABILITY To DRIVE And USE MACHINES:
Methyldopa may cause sedation, usually transient, it may occur during the initial period of therapy or whenever the dose is increased. If affected, patients should not carry out activities where alertness is necessary, such as driving a car or operating machinery.
8-PREGNANCY and LACTATION:
Methyldopa crosses the placental barrier and appears in cord blood and breast milk. 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 or who are breast-feeding their newborn infant requires that anticipated benefits be weighed against possible risks.
9-DRUG INTERACTIONS:
- When methyldopa and lithium are given concomitantly the patient should be monitored carefully for symptoms of lithium toxicity.
- When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive action may occur. The antihypertensive effect of methyldopa may be diminished by sympathomimetics, phenothiazines, tricyclic antidepressants and MAOIs. In addition, phenothiazines may have additive hypertensive effects.
- Several studies demonstrate a decrease in the bioavailability of methyldopa when it is ingested with ferrous sulphate or ferrous gluconate.
10-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 by colorimetric method
As methyldopa fluoresces at the same wavelengths as catecholamines, spuriously high amounts of urinary catecholamines may be reported interfering with a diagnosis of catecholamine-secreting tumours such as phaeochromocytoma or paraganglioma. It is important to recognise this phenomenon before a patient with a possible phaeochromocytoma is subjected to surgery
11-SIDE EFFECTS:
Cardiac disorders: Bradycardia, angina pectoris, myocarditis, pericarditis.
Blood and lymphatic system disorders: Haemolytic anaemia, bone-marrow failure, leucopenia, granulocytopenia, thrombocytopenia, eosinophilia.
Nervous system disorders: Sedation (usually transient), headache, paraesthesia, Parkinsonism, Bell's palsy, involuntary choreoathetotic movements, Impaired mental acuity, carotid sinus syndrome, Dizziness and symptoms of cerebrovascular insufficiency.
Respiratory disorders: Nasal congestion.
Gastrointestinal disorders: Nausea, vomiting, distension, constipation, flatus, diarrhoea, colitis, mild dryness of mouth, sore or 'black' tongue, pancreatitis, sialadenitis.
Skin disorders: Rash as in eczema or lichenoid eruption, toxic epidermal necrolysis.
Musculoskeletal disorders: Lupus-like syndrome, mild arthralgia with or without joint swelling, myalgia.
Endocrine disorders: Hyperprolactinaemia.
Vascular disorders: Orthostatic hypotension.
General disorders: Asthenia or weakness, oedema (and weight gain) usually relieved by use of a diuretic. (Discontinue methyldopa if oedema progresses or signs of heart failure appear.), drug-related fever.
Hepatobiliary disorders: Liver disorders including hepatitis.
Reproductive system disorders: Breast enlargement, gynaecomastia, amenorrhoea, lactation disorders , failure of ejaculation , impotence .
Psychiatric disorders: Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido.
12-DOSAGE & ADMINISTRATION:
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 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 the therapy is followed by return of hypertension, usually within 48 hours.
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 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.
When 500 mg of methyldopa is added to 50 mg of hydrochlorothiazide, the two agents may be given together once daily.
Paediatric population: Initial dosage is 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.
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.
13-OVERDOSAGE:
Acute overdosage may produce acute hypotension with other responses attribute to brain and gastro-intestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, lightheadedness, constipation, distension, flatus, diarrhea, nausea, and vomiting).
If ingestion is recent, emesis may be induced or gastric lavage performed. There is no specific antidote. Methyldopa is dialysable. Treatment is symptomatic.
14-PACKAGING:
HYPOJIT 125- Film Coated Tablets: Carton package of 20 F.C.tablets in blister.
HYPOJIT 250- Film Coated Tablets: Carton package of 20 F.C.tablets in blister.
15-STORAGE CONDITIONS:
Store HYPOJIT - Film Coated Tablets at temperature between (15-30)°C.
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