Presentation and Status in Health Basket
28 X 2.5 mg / 12.5 mg
28 X 5 mg / 25 mg
It is recommended to take this drug once a day, at the same time of the day, usually in the morning.
Adults: The dose should be individualised according to the patient profile and blood pressure control. The administration of the fixed combination of ramipril and hydrochlorothiazide is usually recommended after dosage titration with one of the individual components. This drug should be started at the lowest available dosage. If necessary, the dose can be progressively increased to achieve target blood pressure; the maximum permitted doses are 10 mg
of ramipril and 25 mg of hydrochlorothiazide daily.
Special populations: Diuretic-treated patients In patients concurrently treated with diuretics, as hypotension may occur following initiation of the treatment, caution is recommended. Consideration must be given to reducing the diuretic dose or discontinuing the diuretic before starting treatment.
Patients with renal impairment: This drug is contraindicated in severe renal impairment due to the hydrochlorothiazide component (creatinine clearance < 30 ml/min). Patients with impairment of renal function may require reduced doses. Patients with creatinine clearance levels between 30 and 60 ml/min should only be treated with the lowest fixed dose combination of ramipril and hydrochlorothiazide after administration of ramipril alone. The maximum permitted doses are 5 mg of ramipril and 25 mg of hydrochlorothiazide daily.
Patients with hepatic impairment: In patients with mild to moderate hepatic impairment, treatment must be initiated only under close medical supervision and the maximum daily doses are 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide.This drug is contraindicated in severe hepatic impairment.
Elderly: Initial doses should be lower and subsequent dose titration should be more gradual because of greater chance of undesirable effects especially in very old and frail patients.
Paediatric population: This drug is not recommended for use in children and adolescents below 18 years of age due to insufficient data on safety and efficacy.
Treatment of hypertension. This fixed dose combination is indicated in patients whose blood pressure is not adequately controlled with ramipril alone or hydrochlorothiazide alone.
– Hypersensitivity to the active substance or to any other ACE (Angiotensin Converting Enzyme) inhibitor, hydrochlorothiazide, other thiazide diuretics, sulfonamides or any of the excipients.
– History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs) – Extracorporeal treatments leading to contact of blood with negatively charged surfaces.
– Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney
– 2nd and 3rd trimester of pregnancy.
– Severe impairment of renal function with a creatinine clearance below 30 ml/min in undialysed patients.
– Clinically relevant electrolyte disturbances which may worsen following treatment.
– Severe impairment of liver function, hepatic encephalopathy.
-with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment (creatinine clearance <60 ml/min), with angiotensin-II receptor antagonists (AIIRAs) in patients with diabetic nephropathy.
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Pregnancy: ACE inhibitors such as ramipril, or Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued ACE inhibitor/ AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/ AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
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The safety profile of ramipril + hydrochlorothiazide includes adverse reactions occurring in the context of hypotension and/or fluid depletion due to increased diuresis. The ramipril active substance may induce persistent dry cough, while the hydrochlorothiazide active substance may lead to worsening of glucose, lipid and uric acid metabolism. The two active substances have inverse effects on plasma potassium. Serious adverse reactions include angioedema or anaphylactic reaction, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.
See prescribing information for full details.
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosteronesystem (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
Contra-indicated combinations: Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions. If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.
The combination of TRITACE COMP with aliskiren-containing medicines is
contraindicated in patients with diabetes mellitus or with moderate to severe renal impairment and is not recommended in other patients.
Angiotensin-II Receptor Antagonists (AIIRAs): the use of TRITACE COMP in
combination with an AIIRA is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
For combinations requiring particular caution – please see prescribing information.
Pregnancy and Lactation
Pregnancy: This drug is not recommended during the first trimester of pregnancy and contraindicated during the second and third trimesters of pregnancy. Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started. ACE inhibitor/ Angiotensin II Receptor Antagonist (AIIRA) therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia.
Hydrochlorothiazide, in cases of prolonged exposure during the third trimester of pregnancy, may cause a foeto-placental ischaemia and risk of growth retardation.
Moreover, rare cases of hypoglycaemia and thrombocytopenia in neonates have been reported in case of exposure near term. Hydrochlorothiazide can reduce plasma volume as well as the uteroplacental blood flow.
Lactation: This drug is contraindicated during breast-feeding. Ramipril and hydrochlorothiazide are excreted in breast milk to such an extent that effects on the suckling child are likely if therapeutic doses of ramipril and
hydrochlorothiazide are administered to breast-feeding women. Insufficient information is available regarding the use of ramipril during breast-feeding and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant. Hydrochlorothiazide is excreted in human milk. Thiazides during breast-feeding by lactating mothers have been associated with a decrease or even suppression of lactation. Hypersensitivity to sulphonamide-derived active substances, hypokalaemia and nuclear icterus might occur. Because of the potential for serious reactions in nursing infants from both active substances, a decision should be made whether to discontinue nursing or to discontinue therapy taking account of the importance of this therapy to the mother.
Symptoms associated with overdose of ACE inhibitors may include excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, renal failure, cardiac arrhythmia, impairment of consciousness including coma, cerebral convulsions, pareses, and paralytic ileus. In predisposed patients (e.g. prostatic hyperplasia) hydrochlorothiazide overdose may induce acute urinary retention. The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramiprilat, the active metabolite of ramipril is poorly removed from the general circulation by haemodialysis.