Hydralazine Tablets BP 50mg

1. Name Of The Medicinal Product

HYDRALAZINE TABLETS BP 50mg

2. Qualitative And Quantitative Composition

Each tablet contains 50mg Hydralazine Hydrochloride.

For excipients, see 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Pink, circular, biconvex, film-coated tablets impressed “C” on one face and the identifying letters “HZ” on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Hydralazine is indicated for:

1) Moderate to severe hypertension (in conjunction with a beta-adrenoceptor blocking agent or diuretic) and hypertensive crisis.

2) The management of moderate to severe congestive cardiac failure (reduces afterload), where optimal doses of diuretics and cardiac glycosides prove insufficient. In patients with high left ventricular filling pressure, it is recommended to combine hydralazine with a nitrate.

4.2 Posology And Method Of Administration

For oral administration.

Adults: Dosage should not be increased beyond 100mg daily without first checking the patient's acetylator status.

Hypertension: The dose should be adjusted to the individual requirements of the patient. Treatment should begin with low doses of hydralazine which, depending on the patient's response should be increased stepwise to achieve optimal therapeutic effect whilst keeping unwanted effects to a minimum. Initially 50mg once daily. This can be increased gradually to a dose not exceeding 200mg daily.

Chronic congestive heart failure: Treatment with hydralazine should always be initiated in hospital, where the patients individual haemodynamic values can be reliably determined with the help of invasive monitoring. It should then be continued in hospital until the patient has become stabilised on the requisite maintenance dose. Doses vary greatly between individual patients and are generally higher than those used for treating hypertension. After progressive titration (initially 50mg twice daily) the maintenance dosage averages 50mg four times daily.

Children: Not recommended for this age group.

Elderly: Clinical evidence indicates that no special dosage regime is necessary. Advancing age does not affect either blood concentration or systemic clearance. Renal elimination may however be affected in so far as kidney function diminishes with age.

4.3 Contraindications

Hydralazine should not be given to patients with tachycardia and also in cases of left ventricular failure due to severe aortic or mitral stenosis or in constrictive pericarditis; in heart failure associated with high output (ie in thyrotoxicosis); isolated right ventricular failure due to pulmonary hypertension (ie cor pulmonale); hypersensitivity to hydralazine and dihydralazine or to any of the excipients. Idiopathic system lupus erythematosus (SLE) and related diseases. Dissecting aortic aneurism. Porphyria.

4.4 Special Warnings And Precautions For Use

Use with caution in patients with coronary disease (may provoke angina), in those undergoing anaesthesia (which may precipitate severe hypotension) or in patients with cerebrovascular disease.

Avoid after myocardial infarction until stabilised.

During long-term therapy with hydralazine, it is advisable to determine the antinuclear factors and conduct urinalysis (for microhaematuria and proteinuria) at intervals of approximately 6 months. In the event of positive findings for antinucuclear factors, the titres should be monitored more frequently. At the first signs or symptoms suggestive of SLE or renal disease, hydralazine should be withdrawn, (see also under “other undesirable effects”).

In severe renal failure the interval between doses should be prolonged to avoid accumulation; also in hepatic dysfunction a reduction in dosage or prolonged dosage interval may be indicated.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Potentiation of effects: Concurrent treatment with other antihypertensives, muscle relaxants (baclofen and tizonidine), nitrates, anaesthetics, minor tranquillisers, antidepressants, levodopa or drugs exerting a central depressant action (including alcohol).

Reduction in effects: Concomitant treatment with sympathomimetics, tricyclic antidepressants or MAOI's, NSAIDs, corticosteroids.

4.6 Pregnancy And Lactation

Due to the discovery that hydralazine has a teratogenic effect in mice, causing a small incidence of cleft palate and certain other minor bone malformations in doses ranging from 20-120mg/kg; its use should be avoided in pregnancy during the period of organogenesis, that is the first half of pregnancy. Hydralazine crosses the placental barrier and is excreted in breast milk. Mothers who are receiving hydralazine should not therefore breast feed their infants.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Tachycardia, palpitations, headache, flushing, dizziness, anorexia, angina, nasal congestion, nausea and vomiting can occur, but may be minimised by the prior administration of a beta blocker. Fluid retention.

Patients may occasionally develop symptoms suggestive of rheumatoid arthritis. Skin reactions and fever may occur producing a syndrome similar to systemic lupus erythematosus. This is more likely to occur with high dosage regimes (more than 200mg daily). If such symptoms develop the drug should be gradually withdrawn, when remission will usually occur.

Rarely: Anaemia, leucopenia, neutropenia, thrombocytopenia with or without purpura, proteinuria, increased plasma creatinine, haematuria, dyspnoea and pleural pain.

Isolated cases: Haemolytic anaemia, leucocytosis, lymphadenopathy, pancytopenia, splenomegaly, agranulocytosis.

Occasionally liver damage may occur resembling a hepatitis-like syndrome which is reversible on withdrawal of the drug. Isolated cases of glomerulonephritis have been reported. Hydralazine should be withdrawn if anxiety, depression, febrile reactions, change in blood count or skin rash occur. Rare cases of peripheral neuritis, causing paraesthesia, may be reversed by the administration of pyridoxine, or by withdrawal of hydralazine.

4.9 Overdose

Symptoms including hypotension, tachycardia, myocardial ischaemia, dysrrhythmias and coma.

Gastric lavage or, in the absence of coma, emetic treatment should be given as soon as possible. If hypotension is present, an attempt should be made to raise blood pressure without increasing tachycardia, hence adrenaline (epinephrine) should be avoided. Supportive measures such as intravenous fluids and elevation of foot of bed are also indicated. Cautious administration of angiotensin or noradrenaline (norepinephrine) intravenously may be of use.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Hydralazine hydrochloride is a vasodilator and antihypertensive agent.

Hydralazine is a direct acting vasodilator which exerts a moderate but significant antihypertensive effect (diastolic more than systolic) principally on the arterioles. It tends to improve the renal, uterine and cerebral blood flow. The effect results in a decrease in arterial blood pressure and peripheral vascular resistance, and an increase in heart rate, reflex tachycardia, stroke volume and cardiac output. The rise in cardiac output accompanies the fall in blood pressure, probably as a reflex response; (hydralazine also serves to improve renal blood flow and renal function). Hydralazine lowers blood pressure seemingly by exerting an arteriolar dilating effect through a direct relaxation of vascular smooth muscle.

In heart failure cardiac output is improved as a result of the afterload reduction which is induced by hydralazine; tachycardia or hypotension are seldom seen in this group.

5.2 Pharmacokinetic Properties

Hydralazine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations have been reported to occur in the plasma after about one hour. It is metabolised by hydroxylation of the ring system and conjugation with glucuronic acid, and by N-acetylation.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The tablet core contains: polyvidone, disodium edetate, microcrystalline cellulose (E460), magnesium stearate.

The coating contains: hypromellose (E464), titanium dioxide (E171), polyethylene glycol, carmoisine aluminium lake azorubine (E122).

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Polypropylene and polyethylene containers

Do not store above 25°C. Store in the original container.

Blister packs

Do not store above 25°C. Keep container in the outer carton.

6.5 Nature And Contents Of Container

The product containers are rigid injection moulded polypropylene containers and snap-on polyethylene lids.

The product may also be supplied in blister packs and cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: 250µm white rigid PVC. Surface printed 20µm hard temper aluminium foil with 5-6g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 250s, 500s, 1000s.

Polyethylene container with a polypropylene lid.

Pack size: 56s

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Actavis UK Limited (Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 00142/0500

9. Date Of First Authorisation/Renewal Of The Authorisation

6 March 2001

Renewed – 19.03.09

10. Date Of Revision Of The Text

08/07/2009