- Drugs List
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Tablets containing 5mg imidapril hydrochloride
Tablets containing 10mg imidapril hydrochloride
Tablets containing 20mg imidapril hydrochloride
DosageThe tablets should be taken at about the same time of day, about 15 minutes before meals.
A fat-rich meal significantly reduces the absorption of imidapril.
Initially 5mg once daily.
If control of blood pressure has not been achieved after three weeks the dose should be increased to 10mg once daily which has been determined to be the most effective daily dose.
In a small number of patients it might be necessary to increase the daily dose to 20mg or preferably, to consider combination therapy with a diuretic. The maximum recommended dose is 20mg once daily.
The peak hypotensive effect can be observed 6-8 hours after taking imidapril. Achievement of optimal blood pressure reduction may take several weeks in some patients.
Patients with Renal Impairment
Creatinine clearance between 10ml/minute and 29ml/minute: Imidapril not recommended.
Creatinine clearance below 10ml/minute: Imidapril is contraindicated.
The Renal Drug Handbook suggests that for patients with a glomerular filtration rate of below 50 ml/minute the dose is initially 2.5mg daily and adjusted according to response.
Imidapril and its pharmacologically active metabolite, imidaprilat, are predominantly excreted via the kidney. Hyperkalaemia and other side effects are more common in patients with renal impairment.
There is limited experience of imidapril in patients undergoing haemodialysis. In the event that dialysis becomes necessary in patients already taking imidapril high-flux polyacrylonitrile membranes should be avoided as there is a risk of anaphylactoid reactions. Either use another membrane type or switch therapy to an alternative agent belonging to another class of antihypertensive drugs.
Patients with Hepatic Impairment
Additional Dosage Information
A initial dose of 2.5mg daily is recommended if imidapril is used in patients with angina or cerebrovascular disease or in addition to a diuretic.
ACE inhibitors can cause a very rapid fall in blood pressure in volume-depleted patients. Treatment should be initiated with very low doses. If the dose of diuretic is greater than 80mg furosemide daily or equivalent, the ACE inhibitor should be initiated under close supervision and in some patients the dose of diuretic may need to be reduced or the diuretic discontinued at least 24 hours before hand (may not be possible in heart failure - risk of pulmonary oedema). The manufacturers recommend if possible the diuretic should be discontinued temporarily. If high-dose diuretic therapy can not be stopped, close observation is recommended for at least 2 hours or until blood pressure has stabilised.
Patients at risk of first dose hypotension:
Initiation of therapy requires, if possible, correction in salt and/or body fluid deficiencies, and discontinuation of existing diuretic therapy for 2-3 days before ACE inhibition. If this is not possible the starting dose should be 2.5mg once daily.
In hypertensive patients with concomitant cardiac failure symptomatic hypotension can occur. In these patients the initial dose should be 2.5mg daily under close medical supervision (in hospital in the case of severe heart failure).
Patients at high risk for severe acute first dose hypotension should be monitored medically, preferably in hospital, for up to 6-8 hours after the first dose of imidapril and whenever the dose of imidapril or a concomitant diuretic is increased. The initial dose should be 2.5mg. This also applies to patients with angina pectoris and cerebrovascular disease. These patients are at increased risk to experience myocardial infarction or cerebrovascular accident following excessive hypotension.
For oral administration.
The tablets should be taken at about the same time of day, about 15 minutes before meals.
Each tablet may be divided into equal halves.
Breastfeeding - see ' Lactation' section
Pregnancy - see 'Pregnancy' section
Children under 18 years
Severe bilateral renal artery stenosis
Severe unilateral stenosis of a solitary functioning kidney
Hereditary or idiopathic angioedema
History of angioedema associated with previous ACE inhibitor therapy
Renal impairment - creatinine clearance below 30ml/minute
Haemodialysis using high-flux polyacrylonitrile membranes
Prior to low density lipoprotein apheresis
During desensitisation with hymenoptera venom (e.g. bee and wasp venom) - risk of life-threatening anaphylactoid reactions
Precautions and Warnings
Women who become pregnant while taking imidapril should be warned of the potential hazard to the foetus and should discontinue the treatment. Women of child-bearing potential should use adequate contraception - see 'Pregnancy' section.
Low density lipoprotein (LDL) apheresis (with dextran sulfate): ACE inhibitor use should be temporarily withheld to avoid anaphylactoid reactions.
Haemodialysis: an alternative to high flux polyacrylonitrile membranes should be used or therapy changed to a non ACE inhibitor class of antihypertensive drug.
Withhold ACE inhibitor treatment prior to desensitisation with hymenoptera venom (e.g. bee and wasp venom) to avoid life threatening anaphylactoid reactions.
Use with caution in patients with peripheral vascular disease or severe generalised atherosclerosis (may be indicative of patients with silent or undiagnosed renovascular disease).
Imidapril should be initiated under specialist supervision and with close monitoring in:
Known/suspected renovascular disease - use only if essential and monitor renal function
Unstable heart failure
Severe heart failure (with or without associated renal insufficiency)
Pre-existing hypotension (systolic blood pressure below 90mmHg)
Hyponatraemia (plasma sodium concentration below 130mmol/litre)
High dose vasodilator therapy
High or multiple dose diuretics (e.g. more than 80mg furosemide daily or its equivalent)
See ' Additional Dosage' for use of imidapril and concomitant diuretics.
A profound fall in blood pressure may occur after administration of the first dose of imidapril. Risk factors for this complication include volume and/or salt depleted individuals, diuretic therapy (dose reduction of ACE inhibitor and/or discontinuation of diuretic may also be required to prevent associated renal failure), dietary salt restriction, dialysis patients, diarrhoea and/or vomiting or functional renal impairment. Initiate treatment in these patients only under close medical supervision , preferably in hospital. If hypotension occurs place patient in a supine position and replete volume using intravenous normal saline.
Hypotension after the initial dose of imidapril dose not prevent following treatment. Careful dose titration must be employed.
Although no specific data are available, imidapril may cause hypotension or hypotensive shock in patients undergoing major surgery or during anaesthesia. If imidapril cannot be withheld, volume management should be handled with care.
Ischaemic heart disease or cerebrovascular disease- severe hypotension may result in a myocardial infarct or cerebrovascular accident.
Caution in patients with mitral stenosis, aortic stenosis, hypertrophic cardiomyopathy and obstruction in the outflow of the left ventricle.
Use with caution in patients with collagen vascular disease and immunosuppressed patients, (risk of agranulocytosis/neutropenia may be increased). Serious infections unresponsive to antibiotics may occur - advise patients to report any signs of infection. It is advised that a white blood cell count is preformed prior to treatment every 2 weeks during the first 3 months of treatment and periodically thereafter. Withdraw treatment if neutropenia (neutrophils less than 1000 per mm cubed) is detected or suspected.
Hepatic impairment - see 'Dosage: Hepatic impairment' section.
Discontinue treatment if jaundice or a marked elevation of hepatic enzymes occurs (risk of hepatic necrosis)
Use with caution in patients with renal impairment (creatinine clearance between 30ml/minute and 80ml/minute - reduce dose) - see ' Dosage: Renal Impairment' .
Renal function must be monitored before and during treatment in all patients. Renal failure has been associated with ACE inhibitors and has been mainly observed in patients with severe congestive heart failure or underlying renal disease including renal artery stenosis. If recognised promptly and treated, renal failure is usually reversible. Use with caution in patients with bilateral renal artery stenosis or with stenosis of an artery to a solitary functioning kidney. A specialist should be consulted if renal impairment is significantly reduced as a result of treatment with imidapril.
Patients 65 years or over may be more responsive to imidapril. Initiate with lower dose and evaluate renal function prior to treatment.
There is no experience of the use of imidapril in patients with a recent kidney transplantation.
A dry and non-productive cough may develop in patients on imidapril. This disappears after discontinuation.
Monitor serum electrolytes before and during treatment. Elevations of serum potassium may occur. Those at risk of hyperkalaemia include patients with diabetes mellitus, renal insufficiency or those taking concurrent potassium supplements and or potassium sparing diuretics. Frequent monitoring of serum potassium levels is necessary if these agents are used. Advise patients on the problems of salt substitutes/high intake of potassium-rich food.
In patients with diabetes mellitus, glycaemic control should be closely monitored and adjusted if necessary. Concomitant administration with antidiabetic drugs may increase the blood glucose lowering effect.
History of idiopathic or hereditary angioedema.
Discontinues if angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx occurs. Appropriate monitoring should be initiated. Ensure complete resolution of symptoms prior to dismissing the patient. In cases where airway obstruction is likely, appropriate therapy should be given to ensure airway patency.
ACE inhibitors cause a higher rate of angioedema in black patients.
When used as a single therapeutic agent in hypertension, Afro-Caribbean patients may show a reduced therapeutic response.
Patients with primary aldosteronism may not benefit from this treatment.
When driving or operating machinery it should be taken into account that dizziness or weariness may occur
Co-administration of NSAIDs may reduce the antihypertensive effect of ACE inhibitors, increase serum potassium and exacerbate renal impairment. Patients should be advised not to purchase NSAIDs unless on medical advice.
Contains lactose: use with caution in patients with glucose-galactose malabsorption syndrome or lactose intolerance.
Pregnancy and Lactation
The use of imidapril during pregnancy is contraindicated and adequate contraception is recommended for women of childbearing age.
The use of ACE inhibitors is not recommended during the first trimester of pregnancy. No specific data is available for the use of imidapril during pregnancy. However, in theory, imidapril has a similar potential for inducing adverse foetal and neonatal effects to other ACE inhibitors. Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester has not be conclusive: however a small risk can not be excluded. First trimester exposure to ACE inhibitors has been associated with a significantly increased risk of major congenital malformations.
ACE inhibitors are contraindicated during the second and third trimesters of pregnancy as exposure during these trimesters is known to induce human foetal toxicity (decreased renal function, oligohydramnios (and resulting contractures), skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Other toxic effects include hypoxia, pulmonary hypoplasia, renal tubular dysgenesis and anuria requiring dialysis. Evidence of a risk of teratogenicity after first trimester exposure is conflicting, however, the MHRA recommends that a risk cannot be excluded. The MHRA states that the use of ACE inhibitors in late pregnancy has been associated with adverse effects on the kidney and other congenital anomalies, therefore ACE inhibitors should not be used at any stage during of pregnancy unless absolutely necessary and only then after the potential risks and benefits have been discussed with the patient.
If exposure has occurred in the first trimester a detailed ultrasound diagnosis is advisable. Should exposure to an ACE inhibitor have occurred from the second trimester, an ultrasound check of renal function and the skull is recommended.. Exposure to an ACE inhibitor during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy. In cases involving long term prenatal therapy in the second and/ or third trimesters, the foetus should be monitored for the potential development of oligohydramnios, and foetal growth should be assessed with detailed ultrasound scans (Schaefer, 2007). Infants whose mothers have taken ACE inhibitors should be closely monitored for hypotension.
Unless treatment with an ACE inhibitor is considered absolutely essential, women who are planning to become pregnant should be switched to an alternative drug with an established safety record. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started. Guidelines advise that women who are taking ACE for chronic hypertension in pregnancy, or are planning pregnancy, are told that there is an increased risk of congenital abnormalities. If these drugs are taken, other antihypertensive treatments should be discussed and offered. Ideally, treatment with ACE inhibitors will be terminated within 2 working days of notification of pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Licensed in pregnancy? - No, contraindicated.
Recommended for use in pregnancy? - No.
Effects on foetus - ACE inhibitors can cause decreased renal function, oligohydramnios (and resulting contractures), skull ossification retardation, hypoxia, pulmonary hypoplasia, renal tubular dysgenesis and anuria requiring dialysis.
Other information - If pregnancy occurs during treatment, imidapril must be discontinued immediately and an alternative antihypertensive with greater experience in pregnancy should be considered.
The use of imidapril during breastfeeding is contraindicated.
As no information is available for the use of imidapril during breastfeeding, imidapril is not recommended. Alternative treatments with better established safety profiles during breastfeeding are preferable, especially whilst nursing a newborn or preterm infant . The UK Drugs in Lactation Advisory Service state ACE inhibitors should only be administered when the mother and infant can be monitored as there is insufficient data to allow classification as safe. Schaefer comments that accidental prescribing of imidapril does not require limiting of breastfeeding but therapy should be changed. Guidelines advise that women who still need antihypertensive treatment in the post natal period are informed that there is insufficient evidence on the safety in babies receiving breast milk from a mother taking ACE inhibitors other that enalapril and captopril.
The MHRA concludes that although ACE inhibitors are not generally recommended for use by breastfeeding mothers they are not all absolutely contraindicated and some may be prescribed if treatment is considered essential, however ACE inhibitors should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension particularly in preterm infants. The MHRA has stated that imidapril is not recommended during breastfeeding. If ACE inhibitor therapy is considered essential for the mother the use of captopril, enalapril or quinapril may be considered when the infant is older. The infant should be carefully followed up for signs of hypotension should ACE inhibitor treatment be deemed necessary.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Considered suitable or recommended by manufacturer? - No.
Drug substance licensed in infants? - No.
Other information - Other ACE inhibitors with more established safety profiles during breastfeeding are preferable.
Advise patients to avoid driving and or use machinery if feeling dizzy or tired.
Advise women of childbearing age to use adequate contraception during imidapril treatment or consider a change in therapy.
Advise patients that the use of potassium containing salt substitutes or a high intake of potassium rich foods may lead to significant increases in serum potassium.
Advise patients not to take NSAIDs whilst on ACE inhibitor treatment except on medical advice.
Patients with collagen vascular disease or on immunosuppressant therapy should be instructed to report any signs of infection promptly.
Transient ischaemic attack
Acute renal failure
Toxic epidermal necrolysis
Increase in antinuclear antibodies (ANA)
Loss of balance
Increase in blood urea or creatinine
Elevated serum potassium
Decrease in haemoglobin and haematocrit
Reduced platelet count
White blood cell count decreased
Elevation of liver enzymes
Serum bilirubin increased
Increase in creatine phosphokinase - rarely
Elevated amylase levels
Decreased serum albumin
Changes in erythrocyte sedimentation rate
Changes in mood
Upper respiratory tract infection
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
British National Formulary, 61st Edition (2011) Pharmaceutical Press, London.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Summary of product characteristics: Tanatril tablets 5mg, 10mg, 20mg. Mitsubishi Pharma Europe Ltd Ltd. Revised May 2010.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Clinical Knowledge Summaries - Hypertension in pregnancy, published July 2006
Available at https://www.cks.nhs.uk/hypertension_in_pregnancy
Last accessed: June 23, 2011.
MHRA Drug Safety Update: Volume 2, Issue 10, May 2009.
Last accessed: June 23, 2011.
National Electronic Library for Medicines: ACE inhibitors may be inadvisable during early pregnancy
Last accessed: June 23, 2011.
National Institute for Health and Clinical excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107
Last accessed: June 23, 2011.
UK Drugs in Lactation Advisory Service.
Available at: https://www.ukmicentral.nhs.uk/drugpreg/qrg_p1.asp
Last accessed: June 23, 2011.
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