Loniten Tablets 5 mg

L

1. Name Of The Medicinal Product

Loniten® Tablets 5 mg

2. Qualitative And Quantitative Composition

Each Loniten Tablet contains 5 mg minoxidil USP.

3. Pharmaceutical Form

Tablet

4. Clinical Particulars 4.1 Therapeutic Indications

Loniten is indicated for the treatment of severe hypertension.

It should not be used as the sole agent to initiate therapy. It is a peripheral vasodilator and should be given in conjunction with a diuretic, to control salt and water retention, and a beta-adrenergic blocking agent, or appropriate substitute, to control reflex tachycardia.

4.2 Posology And Method Of Administration

Oral Administration

Adults and Patients over 12 years of age: An initial daily dose of 5 mg, which may be given as a single or divided dosage, is recommended. This dose may first be increased to 10 mg daily and subsequent increases should be by increments of 10 mg in the daily dose. Dosage adjustments should be made at intervals of not less than three days, until optimum control of blood pressure is achieved. It is seldom necessary to exceed 50 mg per day although, in exceptional circumstances, doses up to 100 mg per day have been used. Twice-daily dosage is satisfactory. Where diastolic pressure reduction of less than 30 mm Hg is required, once daily dosing has been reported as effective.

Dosage requirements may be lower in dialysis patients. Minoxidil is removed from the blood by dialysis, but its pharmacological action, once established is not reversed. Therefore haemodialysis patients should take Loniten either after or at least two hours before dialysis.

Children: For patients of 12 years of age or under, the initial dose should be 200 micrograms per kilogram (0.2 mg/kg) given as a single or divided daily dosage. Incremental increases of 100-200 micrograms per kilogram (0.1-0.2 mg/kg) in the daily dose are recommended at intervals of not less than three days until optimum blood pressure control has been achieved, or the maximum daily dose of 1.0 mg/kg has been reached.

Rapid reduction of blood pressure: Under hospital monitoring conditions, rapid reduction of blood pressure can be achieved using continuous blood pressure monitoring and incremental doses of 5 mg every six hours.

Concomitant antihypertensive therapy: It is recommended that, where possible, antihypertensive therapy, other than a beta

Loniten causes sodium retention and if used alone can result in several hundred milli-equivalents of salt being retained together with a corresponding volume of water.

Therefore, in all patients who are not on dialysis, Loniten must be given in conjunction with a diuretic in sufficient dosage to maintain salt and water balance. Examples of the daily dosages of diuretics commonly used when starting therapy with Loniten include:

1. Hydrochlorothiazide (100 mg)

2. Chlorthalidone (100 mg).

3. Frusemide (80 mg).

If excessive water retention results in a weight gain of more than 3 pounds when a thiazide or chlorthalidone is being used, diuretic therapy should be changed to frusemide, the dose of which may be increased in accordance with the patient's requirements. Diuretic dosage in children should be proportionally less in relation to weight.

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 pre-treated patients have an increase in heart rate exceeding 20 beats per minute or when simultaneous introduction causes an increase exceeding 10 beats per minute. When beta-blockers are contra-indicated, alternatives such as methyldopa may be used instead and should be started 24 hours prior to Loniten.

Elderly patients: At present there are no extensive clinical studies with minoxidil in patients over age 65. There is data indicating that elevated systolic and diastolic pressures are important risk factors for cardiovascular disease in individuals over age 65. However, elderly patients may be sensitive to the blood pressure lowering effect of minoxidil and thus caution is urged in initiating therapy as orthostatic hypotension may occur. It is suggested that 2.5 mg per day be used as the initial starting dose in patients over 65 years of age.

4.3 Contraindications

Loniten is contra-indicated in patients with a phaeochromocytoma.

4.4 Special Warnings And Precautions For Use

If used alone, Loniten can cause a significant retention of salt and water leading to positive physical signs such as oedema, and to clinical deterioration of some patients with heart failure. Diuretic treatment alone, or in combination with restricted salt intake is, therefore, necessary for all patients taking Loniten.

Patients who have had myocardial infarction should only be treated with Loniten after a stable post-infarction state has been established.

The physician should bear in mind that if not controlled by sympathetic suppressants, the rise in cardiac rate and output that follows the use of potent vasodilators may induce anginal symptoms in patients with undiagnosed coronary artery disease, or may aggravate pre-existing angina pectoris.

The effect of Loniten may be additive to concurrent antihypertensive agents. The interaction of Loniten with sympathetic-blocking agents such as guanethidine or bethanidine may produce excessive blood pressure reduction and/or orthostasis.

Hypertrichosis occurs in most patients treated with Loniten and all patients should be warned of this possibility before starting therapy. Spontaneous reversal to the pre-treatment state can be expected one to three months after cessation of therapy.

Soon after starting Loniten therapy approximately 60% of patients exhibit ECG alterations in the direction and magnitude of their T waves. Large changes may encroach on the ST segment, unaccompanied by evidence of ischaemia. These asymptomatic changes usually disappear with continuing Loniten treatment. The ECG reverts to the pre-treatment state if Loniten is discontinued.

Pericardial effusion has been detected in patients treated with a Loniten-containing regime. A cause and effect relationship has not been established. Most effusions have either been present before Loniten was given, or occurred among uraemic patients. However, it is suggested that Loniten

Salt and water retention in excess of 2 to 3 pounds may diminish the effectiveness of Loniten. Patients should, therefore, be carefully instructed about compliance with diuretic therapy and a detailed record of body weight should be maintained.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The effect of Loniten may be additive to concurrent antihypertensive agents. The interaction of Loniten with sympathetic-blocking agents such as guanethidine or bethanidine may produce excessive blood pressure reduction and/or orthostasis.

4.6 Pregnancy And Lactation

The safety of Loniten in pregnancy remains to be established. Minoxidil has been shown to reduce the conception rate in rats and to show evidence of increased fetal absorption in rabbits. There was no evidence of teratogenic effects in rats and rabbits. Minoxidil has been reported to be secreted in breast milk. Therefore, breast-feeding should not be undertaken while a patient is on Loniten Tablets.

4.7 Effects On Ability To Drive And Use Machines

No adverse effects reported

4.8 Undesirable Effects

Most patients receiving Loniten experience a diminution of pre-existing side effects attributable to their disease or previous therapy. New events or side effects likely to increase include peripheral oedema, associated with or independent of weight gain; increases in heart rate; hypertrichosis; and a temporary rise in creatinine and blood urea nitrogen. Gastro-intestinal intolerance, rash and breast tenderness are infrequently reported side effects of Loniten therapy.

4.9 Overdose

If exaggerated hypotension is encountered, it is most likely to occur in association with residual sympathetic nervous system blockade (guanethidine-like effects or alpha-adrenergic blockade). Recommended treatment is intravenous administration of normal saline. Sympathomimetic drugs, such as noradrenaline or adrenaline, should be avoided because of their excessive cardiac-stimulating action. Phenylephrine, angiotensin II and vasopressin, which reverse the effect of Loniten, should be used only if inadequate perfusion of a vital organ is evident.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Minoxidil is an antihypertensive agent which acts predominantly by causing direct peripheral vasodilation of the arterioles.

5.2 Pharmacokinetic Properties

About 90% of an oral dose of minoxidil has been reported to associated from the GI tract.

Following oral administration the maximum hypotensive effect usually occurs after 2-3 hours. The action may persist for up to 75 hours. The plasma half-life is about 4.2 hours.

Minoxidil is not bound to plasma proteins. It is extensively metabolised in the liver primarily by conjugation with glucuronic acid and is excreted in the urine mainly in the form of metabolites.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactose hydrous, microcrystalline cellulose, starch, colloidal silicon dioxide and magnesium stearate.

6.2 Incompatibilities

None

6.3 Shelf Life

Shelf life of the medicinal product as packaged for sale: 36 months.

6.4 Special Precautions For Storage

Store below 25oC.

6.5 Nature And Contents Of Container

High density polyethylene (HDPE) bottles with LDPE caps. Each bottle contains 100 tablets.

20-25 micron aluminium foil/250 micron opaque PVC blister. Pack contains 60 tablets.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Pharmacia Limited

Davy Avenue

Milton Keynes

MK5 8PH

UK

8. Marketing Authorisation Number(S)

PL 0032/0065

9. Date Of First Authorisation/Renewal Of The Authorisation

14 November 1979/17 September 2005

10. Date Of Revision Of The Text

April 2001

Legal Category

POM

Loniten Tablets 5 mg

.