HYDRAZALINE Film-coated tablet Ref.[8218] Active ingredients: Hydralazine

Warnings

The overall ‘hyperdynamic’ state of the circulation induced by hydralazine may accentuate certain clinical conditions. Myocardial stimulation may provoke or aggravate angina pectoris. Patients with suspected or confirmed coronary artery disease should therefore be given Hydralazine 25mg Tablets BP only under cover of beta-blocker or in combination with other suitable sympatholytic agents. It is important that the beta-blocker medication should be commenced a few days before the start of treatment with Hydralazine 25mg Tablets BP.

Patients who have survived a myocardial infarction should not receive Hydralazine 25mg Tablets BP until a post-infarction stabilisation state has been achieved.

Prolonged treatment with hydralazine (i.e. usually for more than 6 months) may provoke a systemic lupus erythematosus (SLE)-like syndrome, especially where doses exceed 100 mg daily. First symptoms are likely to be similar to rheumatoid arthritis (arthralgia, sometimes associated with fever, anaemia, leucopenia, thrombocytopenia and rash) and are reversible after withdrawal of the drug. In its more severe form it resembles acute SLE (similar manifestations as the milder form plus pleurisy, pleural effusions and pericarditis), and in rare cases renal and ocular involvement have been reported. Early detection and a timely diagnosis with appropriate therapy (i.e. treatment discontinuation and possibly long-term treatment with corticosteroids may be required to reverse these changes) are of utmost importance in this life-threatening illness to prevent more severe complications, which may sometimes be fatal.

Since such reactions tend to occur more frequently the higher the dose and the longer its duration, and since they are also more common in slow acetylators, it is recommended that for maintenance therapy the lowest effective dose should be used. If 100 mg daily fails to elicit an adequate clinical effect, the patient’s acetylator status should be evaluated. Slow acetylators and women run greater risk of developing the SLE-like syndrome and every effort should therefore be made to keep the dosage below 100 mg daily and a careful watch kept for signs and symptoms suggestive of this syndrome. If such symptoms do develop the drug should be gradually withdrawn.

Rapid acetylators often respond inadequately even to doses of 100 mg daily and therefore the dose can be raised with only a slightly increased risk of an LE like syndrome.

During long term treatment with Hydralazine 25mg Tablets BP it is advisable to determine the antinuclear factors and conduct urine analysis at intervals of approximately 6 months. Microhaematuria and/or proteinuria, in particular together with positive titres of ANF, may be initial signs of immune-complex glomerulonephritis associated with the SLE like syndrome. If overt clinical signs or symptoms develop, the drug should be withdrawn immediately.

Skin rash, febrile reactions and change in blood count occur rarely and drug should be withdrawn. Peripheral neuritis in the form of paraesthesia has been reported, and may respond to pyridoxine administration or drug withdrawal.

Precautions

In patients with renal impairment (creatinine clearance <30 ml/min or serum creatinine concentrations >2.5 mg/100 ml or 221 μmol/l) and in patients with hepatic dysfunction the dose or interval between doses should be adjusted according to clinical response, in order to avoid accumulation of the ‘apparent’ active substance.

Hydralazine 25mg Tablets BP should be used with caution in patients with coronary artery disease (since it may increase angina) or cerebrovascular disease.

When undergoing surgery, patients treated with Hydralazine 25mg Tablets BP may show a fall in blood pressure, in which case one should not use adrenaline to correct the hypotension, since it enhances the cardiac-accelerating effects of hydralazine.

When initiating therapy in heart failure, particular caution should be exercised and the patient kept under surveillance and/or haemodynamic monitoring for early detection of postural hypotension or tachycardia. Where discontinuation of therapy in heart failure is indicated, Hydralazine 25mg Tablets BP should be withdrawn gradually (except in serious situations, such as SLE-like syndrome or blood dyscrasias) in order to avoid precipitation and/or exacerbation of heart failure.

Lactose

Patients with rare hereditary problems of galactose intolerance, total lactose deficiency or glucose-galactose malabsorption should not take this medicine.

Potentiation of effects

Concurrent therapy with other antihypertensives (vasodilators, calcium antagonists, ACE inhibitors, diuretics), muscle relaxants (baclofen and tizonidine), anaesthetics, tricyclic antidepressants, major tranquillisers, nitrates or drugs exerting central depressant actions (including alcohol).

Administration of Hydralazine 25mg Tablets BP shortly before or after diazoxide may give rise to marked hypotension.

MAO inhibitors should be used with caution in patients receiving Hydralazine 25mg Tablets BP.

Concurrent administration of Hydralazine 25mg Tablets BP with beta-blockers subject to a strong first pass effect (e.g. propranolol) may increase their bioavailability. Downward adjustment of these drugs may be required when they are given concomitantly with Hydralazine 25mg Tablets BP.

There is potential for the hypotensive effect of hydralazine to be antagonised when used concomitantly with oestrogens or non-steroidal anti-inflammatory drugs.

Reduction in effects

Concomitant treatment with sympathomimetics, tricyclic antidepressants, NSAIDs, corticosteroids.

Pregnancy

Use of Hydralazine in pregnancy, before the third trimester should be avoided but the drug may be employed in later pregnancy if there is no safer alternative or when the disease itself carries serious risks for the mother or child e.g. pre-eclampsia and or eclampsia.

No serious adverse effects in human pregnancy have been reported to date with Hydralazine, although experience in the third trimester is extensive.

Breast-feeding

Hydralazine passes into breast milk but reports available so far have not shown adverse effects on the infant Mothers in whom use of Hydralazine is unavoidable may breast feed their infant provided that the infant is observed for possible adverse effects.

Hydralazine may impair the patient’s reactions especially at the start of the treatment.

The patient should be warned of the hazard when driving or operating machinery.

Some of the adverse effects listed below e.g. tachycardia, palpitations, angina symptoms, flushing, headache, dizziness, nasal congestion and gastro-intestinal disturbances are commonly seen at the start of treatment, especially if the dose is raised quickly. However such effects generally subside in the further course of treatment.

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)

Blood and lymphatic system disorders

Uncommon: anaemia, leucopenia, neutropenia, thrombocytopenia with or without purpura

Rare: haemolytic anaemia, leucocytosis, lymphadenopathy, pancytopenia, splenomegaly, agranulocytosis

Psychiatric disorders

Uncommon: agitation, anorexia, anxiety

Rare: depression, hallucinations

Nervous system disorder

Very common: headache

Uncommon: dizziness

Rare: peripheral neuritis, polyneuritis, paraesthesiae (these unwanted effects may be reversed by administering pyridoxine)

Eye disorders

Uncommon: increased lacrimation, conjunctivitis

Cardiac disorders

Very common: tachycardia, palpitations

Common: flushing, hypotension, anginal symptoms

Uncommon: oedema, heart failure

Rare: paradoxical pressor responses, fluid retention

Respiratory, thoracic and mediastinal disorders

Uncommon: nasal congestion, dyspnoea, pleural pain

Gastrointestinal disorders

Common: gastro-intestinal disturbances, diarrhoea, nausea, vomiting

Uncommon: jaundice, liver enlargement, abnormal liver function sometimes in association with hepatitis

Rare: paralytic ileus

Skin and subcutaneous tissue disorders

Uncommon: rash

Musculoskeletal and connective tissue disorders

Common: arthralgia, joint swelling, myalgia

Renal and Urinary disorders

Uncommon: proteinuria, increased plasma creatinine, haematuria sometimes in association with glomerulonephritis

Rare: acute renal failure, urinary retention, glomerulonephritis

General disorders and administration site conditions

Common: SLE-like syndrome (sometimes resulting in a fatal outcome. See section 4.4)

Uncommon: hypersensitivity reactions such as pruritus, urticaria, vasculitis, eosinophilia, hepatitis, fever, weight decrease, malaise, anti-neutrophil cytoplasmic antibody positive vasculitis

Rare: exophthalmos, rheumatoid arthritis

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.