HYDRALAZINE

Posology Elderly:

Clinical evidence would indicate 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.

Adults:

Initially 5 to 10 mg by slow intravenous injection, to avoid precipitous decreases in arterial pressure with a critical reduction in cerebral or utero-placental perfusion. If necessary, a repeat injection can be given after an interval of 20-30 minutes, throughout which blood pressure and heart rate should be monitored.

A satisfactory response can be defined as a decrease in diastolic blood pressure to 90/100 mmHg. Method of Administration The contents of the vial should be reconstituted by dissolving in 1 ml of water for injection BP. 9% and be administered by slow intravenous injection.

The injection must be given immediately, and any remainder discarded. Hydralazine may also be given by continuous intravenous infusion, beginning with a flow rate of 200- 300μg/min. Maintenance flow rates must be determined individually and are usually within the range 50-150μg/min.

9% and given by continuous infusion. The addition should be made immediately before administration and the mixture should not be stored. Hydralazine for infusion can also be used with 5% sorbitol solution or isotonic inorganic infusion solutions such as Ringers solution.

Paediatric population:

The safety and efficacy of Apresoline 20 mg Ampoules / Hydralazine 20mg Powder for Concentrate for Solution for Injection/Infusion in children have not yet been established. Method of administration For Intravenous use only. 4).

Adverse drug reactions from multiple sources including clinical trials and spontaneous reports are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first.

Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. 001%), not known (cannot be estimated from the available data). 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. System Organ Class Frequency Adverse effects Rare Anaemia, leucopenia, neutropenia, thrombocytopenia with or without purpura. eosinophilia Blood and lymphatic system disorders Isolated cases Haemolytic anaemia, leucocytosis, lymphadenopathy, pancytopenia, splenomegaly agranulocytosis Metabolism and nutrition disorders Rare Anorexia Rare Agitation, anxietyPsychiatric disorders Isolated cases Depression, hallucinations Very common Headache Rare Dizziness Isolated cases Peripheral neuritis, polyneuritis, paraesthesia (these unwanted effects may be reversed by administering pyridoxine).

Nervous system disorders Not known:

Tremor Rare Conjunctivitis, lacrimation increasedEye disorders Isolated cases Exophthalmos Cardiac disorders Very common: Tachycardia, palpitations Common Anginal pectoris Rare heart failure Common Flushing, hypotensionVascular disorder Isolated cases: Paradoxical pressor responses Respiratory, thoracic and mediastinal disorders Rare Nasal congestion, Dyspnoea, pleuritic pain Common Gastrointestinal disturbances, diarrhoea, nausea vomiting Gastrointestinal disorders Isolated cases Paralytic ileus.

Rare Jaundice, hepatomegaly, abnormal liver functio sometimes in association with hepatitis. 4 Special warnings and precautions for use) Skin and subcutaneous tissue disorders Rare Hypersensitivity reactions such as pruritus, urticaria, vasculitis, rash Musculoskeletal and connective tissue disorders Common Arthralgia, joint swelling, myalgia Rare Proteinuria, Blood creatinine increased, haematuria sometimes in association with glomerulonephritis.

Renal and urinary disorders Isolated cases Acute kidney failure, urinary retention. General disorders and administration site conditions Rare Pyrexia, malaise, Oedema. Investigations Rare Weight decrease 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Cardiovascular system The overall 'hyperdynamic' state of the circulation induced by hydralazine may accentuate certain clinical conditions. Myocardial stimulation may provoke or aggravate angina pectoris. Hydralazine can cause anginal attacks and ECG changes indicative of myocardial ischaemia.

It must therefore be used with caution in patients with suspected coronary artery disease or with cerebrovascular disease. Patients with suspected or confirmed coronary artery disease should therefore be given Hydralazine only under beta-blocker cover 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. When undergoing surgery, patients treated with /Hydralazine 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.

Patients who have survived a myocardial infarction should not receive Hydralazine until a post-infarction stabilisation phase has been achieved. 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 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.

Immune system Prolonged treatment with hydralazine may provoke a systemic lupus erythematosus (SLE)-like syndrome. 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. 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 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 SLE-like syndrome.

During long-term treatment with Hydralazine, 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. A complete blood count and ANF titre determination is indicated before and periodically during prolonged therapy with hydralazine even if the patient is asymptomatic.

These studies are also indicated if the patient develops arthralgia, fever, chest pain, persistent malaise, or other unexplained signs or symptoms. A positive ANF titre requires that the physician carefully weighs the implications of the test results against the benefits of continued therapy with hydralazine.

Nervous system Isolated cases of Peripheral neuritis in the form of paraesthesia has been reported, and may respond to pyridoxine administration or drug withdrawal. 2). Haematological effects Adverse haematological effects, such as a reduction in haemoglobin and red cell count, leucopoenia, agranulocytosis and purpura, have been reported in a very few cases.

If such abnormalities develop, therapy should be discontinued. Genetic effects In high (cyto-) toxic concentrations, hydralazine induces gene mutations in single cell organisms and in mammalian cells in vitro. No unequivocally mutagenic effects have been detected in vivo in a great number of test systems.

Skin Skin rash, febrile reactions and change in blood count occur rarely and drug should be withdrawn. Driving and using machines Dizziness or hypotension may occur with Apresoline with established mechanism of action, it is therefore advisable to exercise caution when driving or operating machinery.

1. Known hypersensitivity to dihydralazine. Idiopathic systemic lupus erythematosus (SLE) and related diseases. g. in thyrotoxicosis). g. in the presence of aortic or mitral stenosis or constrictive pericarditis). Isolated right ventricular failure due to pulmonary hypertension (cor pulmonale).

Dissecting aortic aneurysm. Porphyria