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LONITEN® 5,0 mg Tablets
LONITEN® 10,0 mg Tablets

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

LONITEN® 5,0 mg Tablets
LONITEN® 10,0 mg Tablets

COMPOSITION :
LONITEN 5 mg tablets contain minoxidil 5 mg per tablet
LONITEN 10 mg tablets contain minoxidil 10 mg per tablet

PHARMACOLOGICAL CLASSIFICATION:
A 7.1 Vasodilators, hypertensive medicines

PHARMACOLOGICAL ACTION:
LONITEN selectively relaxes smooth muscle which reduces peripheral vascular resistance and lowers systemic blood pressure. This is accomplished without a diminution of nutritional flow to body tissues or interference with normal vasomotor reflexes.
LONITEN does not directly stimulate the heart or electrolyte reabsorption of the kidney. However, LONITEN administration elicits a reflex mediated increase in cardiac output; salt and water retention; and a rise in plasma renin activity. These effects are diminished by the simultaneous administration of diuretics and beta-adrenergic blocking agents.
Gastro-intestinal absorption is rapid and amounts to at least 95% of the administered dose. Serum levels of the parent drug peak within the first hour. The plasma elimination half-life of LONITEN is approximately 4 - 4,5 hours but the duration of its hypotensive action may exceed 24 hours. This disparity between blood level and pharmacological effect, and the large volume of distribution induces extensive tissue localisation of the drug.
However, on chronic treatment, accumulation does not occur and the pharmacological effect is slowly reversible. With an effective oral dose, blood pressure usually starts to decline within one-half hour, reaches a minimum between 2 and 3 hours, and recovers at a rate of approximately 30% per day.
During daily administration, there is a cumulative effect which reaches a steady state after 3 to 7 days. The magnitude of the blood pressure response is related to the extent of the original diastolic elevation above 85 mmHg, and is proportional to the logarithmic function of dose administered. When the desired diastolic reduction is greater than 30 mmHg, twice a day dosing is advised to keep the diurnal variation within 10 mmHg.
LONITEN does not bind to plasma proteins, or enter the central nervous system or accumulate in body tissues. Metabolism is predominantly by glucuronic acid conjugation.
Metabolites are excreted principally in the urine and can be removed by haemodialysis in anephric patients. Haemodialysis does not, however, rapidly reverse LONITEN’s pharmacologic effect.

INDICATIONS:
Indicated as adjunctive therapy in adults with severe refractory hypertension which has failed to respond to extensive multiple therapy. LONITEN should be used concurrently with a sympathetic nervous system suppressant and a diuretic to initiate therapy.

CONTRA-INDICATIONS:
Pulmonary hypertension associated with mitral stenosis and known hypersensitivity to minoxidil. LONITEN is contra-indicated in pheochromocytoma.
Safety in pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE:
The usual adult dosage range of LONITEN is 5 to 40 mg/day. The maximum recommended dosage is 100 mg/day.
LONITEN therapy can be initiated with a single or divided daily dosage. If the desired reduction in diastolic pressure is greater than 30 mmHg, divided dosage will minimize diurnal fluctuations. Dosage adjustments should be made at intervals of 3 days or longer.
A more rapid reduction of pressure can be achieved using continuous blood pressure monitoring and incremental doses of 5 mg every 6 hours. Dosage requirements may be lower in patients undergoing chronic dialysis. Prior to introducing LONITEN, it is recommended that the antihypertensive therapy be adjusted to a regimen consisting of a diuretic and beta-adrenergic blocking agent. When other sympathetic nervous system suppressants are used, the initial dosage of LONITEN should be reduced.
Patients over 12 years of age:
Initial dosage: 5 mg as a single or divided daily dosage.
Incremental increases: 5 - 10 mg/day, at 3-day intervals, until 50 mg/day is reached; then in increments of 25 mg/day up to a maximum of 100 mg/day.
Patients 12 years of age and under:
Initial dosage: 0,2 mg/kg as a single or divided daily dosage.
Incremental increases: 0,1 mg - 0,2 mg/kg/day, at 3-day intervals, up to a maximum of 1 mg/kg/day.
Concomitant therapy:
Diuretics:
LONITEN must be given with sufficient diuretic therapy to maintain salt and water balance in all patients who are on dialysis. When excessive water retention results in a weight gain exceeding 2 kg, the type of diuretic should be changed or an aldosterone antagonist should be added. In children, diuretic dosage should be proportional to body weight.
Sympathetic nervous system suppressants:
Initially, most patients will require a sympathetic nervous system suppressant to limit a LONITEN-induced rise in heart rate.
The preferred agent is a beta-blocker equivalent to an adult propranolol dosage of 80 - 160 mg/day. Higher doses may be required when pretreated patients have an increase in heart rate exceeding 20 beats/minute or when simultaneous introduction causes an increase exceeding 10 beats/minute. When beta-blockers are contra-indicated, methyldopa or clonidine may be used instead and should be started 24 hours prior to LONITEN.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Salt and water retention
If used alone, LONITEN can cause a significant retention of salt and water, producing dependent oedema; puffiness of face, eyes or hands; neck vein distention; hepatomegaly and a positive hepatojugular reflux. Chest X-rays may show evidence of pulmonary vascular engorgement. Minoxidil should be used in combination with a diuretic to prevent fluid retention oedema, and possibly congestive heart failure. The patient’s body mass, fluid and electrolyte balance, should be monitored, and if there is evidence of fluid retention, the more vigorous diuretic treatment alone or in combination with restricted salt intake should be instituted.
Refractoriness to these measures may require temporary discontinuation of LONITEN therapy for 1 or 2 days, during which there may be partial loss of blood pressure control.
Salt and water retention in excess of 2,0 kg of weight gain may diminish the effectiveness of LONITEN, therefore, patients should be carefully instructed about compliance with diuretic usage and limitation of their electrolyte intake.
Tachycardia
Because it is a vasodilator, reflex tachycardia may occur; angina pectoris may develop in patients with unsuspected coronary artery disease unless protected against LONITEN-induced tachycardia with beta-adrenergic blocking drugs or other suitable sympathetic nervous system suppressants.
Patients with unstable angina pectoris or angina pectoris of recent onset should be protected with these agents before starting LONITEN therapy.
Pericarditis, pericardial effusion and tamponade
Pericarditis, pericardial effusion and tamponade, have been observed. LONITEN-treated patients should be periodically monitored for signs of symptoms of these events and, if found, appropriate therapy should be instituted. If the effusion persists, withdrawal of minoxidil should be considered in the light of other means of controlling the hypertension and the patient’s clinical status.
Patients who have had a myocardial infarction should only be treated with LONITEN after a stable post-infarction state has been established.
Renal failure or dialysis patients
Those patients with renal failure or on haemodialysis may require smaller doses of minoxidil.
Dermatologic-hypertrichosis
Elongation, thickening, and enhanced pigmentation of fine body hair has been seen in the majority of patients taking minoxidil. No endocrine abnormalities have been found to explain abnormal hair growth. All patients should be fully informed of this possible effect before commencing LONITEN therapy.
It is usually first noticed in the facial area within 3 to 6 weeks after starting therapy, and may recede slightly during prolonged therapy. Upon discontinuation of minoxidil, new hair growth stops, but it may take one to six months for restoration of pretreatment appearance.
Hypersensitivity
Rashes have been reported, including reports of bullous eruptions, and Stevens-Johnson syndrome.
Altered laboratory findings

a)

ECG changes - A high percentage of patients exhibit ECG alterations in the direction and magnitude of their T-waves soon after starting LONITEN therapy. Large changes may encroach on the ST segment, but the ST segment is not independently altered and there is no evidence of myocardial ischemia. These asymptomatic changes usually disappear with continuing LONITEN treatment. The ECG reverts to the pre-treatment state if LONITEN is discontinued.

b)

Haematologic - Thrombocytopenia and leukopenia have rarely been reported, as well as a temporary decline in haemoglobin and haematocrit, and a temporary rise in creatinine and BUN.

General
Hypotension, gastro-intestinal intolerance, rash and breast tenderness, gynaecomastia and polymenorrhoea may occur.
LONITEN is not recommended for the treatment of patients with labile or mild hypertension.
LONITEN should not be used for extended therapy in hypertension readily ameliorated by surgery, e.g. coarctation of the aorta, primary aldosteronism, or unilateral, large vessel renal artery stenosis.
Interactions
Guanethidine - while minoxidil itself does not cause orthostatic hypotension, its administration to patients already receiving guanethidine can result in profound orthostatic effects. If possible, guanethidine should be discontinued well before minoxidil is begun. If this is not feasible, minoxidil therapy should be instituted in the hospital and the patient monitored carefully for orthostatic events.
The blood pressure lowering effect of LONITEN is additive to concurrent anti-hypertensive agents. The interaction of LONITEN with agents that produce orthostatic hypotension may result in excessive blood pressure reduction.
Use in paediatrics
Use in children has been limited and recommendations under “Dosage and directions for use”can be considered a rough guide at present.
Careful titration is essential.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Hypotension may occur. Recommended treatment is intravenous administration of normal saline. Sympathomimetic agents, such as noradrenaline or adrenaline, should be avoided because of their excessive cardiac-stimulating action. Phenylephrine, angiotensin II, and vasopressin which reverse the effects of LONITEN should only be used if inadequate perfusion of a vital organ is evident.

IDENTIFICATION:
Loniten 5 mg and 10 mg tablets are round white tablets.
Loniten 5 mg tablets are imprinted with a "5" on one side of the tablet with a "U" with a "score" and then "U" on the other side of tablet.
Loniten 10 mg tablets are imprinted with a "10" on one side of the tablet with a "U" with a "score" and then "137" on the other side of tablet.

PRESENTATION:
Bottles of 100 tablets containing 5 mg or 10 mg.

STORAGE INSTRUCTIONS:
Store at room temperature (15° - 30°C). Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
LONITEN 5 mg: N/7.1/165
LONITEN 10 mg: N/7.1/166

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Limited
Alphen West G
George Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
6 September 1990

New addition to this site: February 2005
Source: Pharmaceutical Industry
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