Film – coated tablet
Prescription only medicine
1. PRESENTATION:
Each Tablet contains: Amlodipine (as Besilate) ……5mg
Excipients. Microcrystalline Cellulose, Anhydrous Dibasic Calcium Phosphate, Sodium Starch Glycolate, Magnesium Stearate
Read this leaflet carefully before you start taking this medicine.
- Keep this leaflet you may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
WHAT REMEDIPIN IS AND WHAT IT IS USED FOR
Remedipin is used to treat high blood pressure (hypertension) or a certain type of chest pain called angina, a rare form of which is Prinzmetal’s or variant angina. Remedipin is also indicated in prophylaxis of chronic stable angina pectoris
Remedipin belongs to a group of drugs called calcium antagonists. In patients with high blood pressure Remedipin works by relaxing the blood vessels, so that blood passes through them more easily. In angina the heart receives too little oxygen. Remedipin widens the veins in the heart, so that the heart receives more oxygen and as a result chest pain is prevented.
2. INDICATIONS
Hypertension.
Prophylaxis of chronic stable angina pectoris.
Prinzmetal’s (variant) angina when diagnosed by a cardiologist.
In hypertensive patients, amlodipine has been used in combination with a thiazide diuretic, alpha blocker, beta-adrenoceptor blocking agent, or an angiotensin converting enzyme inhibitor. For angina, Remedipin may be used as monotherapy or in combination with other antianginal drugs in patients with angina that is refractory to nitrates and / or adequate doses of beta blockers.
Amlodipine is well tolerated in patients with heart failure and a history of hypertension or ischaemic heart disease.
3. DOSAGE AND ADMINISTRATION
In adults: For both hypertension and angina the usual initial dose is 5 mg Remedipin once daily which may be increased to a maximum dose of 10 mg depending on the individual patient’s response.
No dose adjustment of Remedipin is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.
Use in children: Not recommended.
Use in the elderly: Remedipin, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore normal dosage regimens are recommended.
Patients with renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.
If you take more Remedipin than you should:
Contact your doctor or emergency department if you have taken more Remedipin than stated in this leaflet or more than the doctor has prescribed. Take this leaflet and any tablets you still have with you.
If you forget to take Remedipin:
If you forgot to take a dose, take it as soon as you remember it unless it is nearly time for your next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Remedipin:
The treatment must only be changed or stopped in consultation with your doctor.
4. CONTRAIDICATIONS
Remedipin is contra-indicated in patients with a known sensitivity to dihydropyridines, amlodipine or any of the excipients.
Remedipin should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina (excluding Prinzmetal’s angina).
5. WARNINGS & PRECAUTIONS:
Use in patients with Heart Failure: In a long-term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure of nonischaemic aetiology, amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.
Use in patients with impaired hepatic function: as with all calcium antagonists, amlodipine’s half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. The drug should therefore be administered with caution in these patients.
There are no data to support the use of amlodipine alone, during or within one month of a myocardial infraction.
The safety and efficacy of amlodipine in hypertensive crisis has not been established.
6. PREGNACY AND LACTATION:
Pregnancy:
Remedipin should not be administered during pregnancy or to women of child bearing potential, unless effective contraception is used.
Ask your doctor or pharmacist for advice before taking this medicine.
Breast-feeding:
Remedipin should not be administered to women who are breast-feeding.
Ask your doctor or pharmacist for advice before taking this medicine.
7. EFFECTS ON ABILITY TO DRIVE OR OPERATE MACHINERY:
Clinical experience with amlodipine indicates that therapy is unlikely to impair a patient’s ability to drive or use machinery.
8. UNDESIRABLE EFFECTS
Like all medicines, Remedipin can cause side effects.
Common side effects (occurring in between 1 and 10 in 100 patients):
Headache, dizziness, somnolence, palpitations, flushing, abdominal pain, nausea, oedema, fatigue.
Uncommon side effects (occurring in between 1 and 10 in 1.000 patients):
Insomnia, mood changes, tremor, taste perversion, syncope, hypoaesthenia, paraesthesia, visual disturbances, tinnitus, hypotension, dyspnoea, rhinitis, vomiting, dyspepsia, dry mouth, alopecia, purpura, skin discolouration, increased sweating, pruritus, rash, arthralgia, myalgia, muscle cramps, back pain, micturition disorder, nocturia, increased urinary frequency, impotence, gynaecomastia, chest pain, asthenia, pain, malaise, weight increase, weight decrease.
Rare side effects (occurring in between 1 and 10 in 10,000 patients):
Thrombocytopenia, allergic reactions, hyperglycaemia, peripheral neuropathy, myocardial infraction, arrhythmia, ventricular tachycardia and atrial fibrillation, vasculitis, coughing, pancreatitis, gastritis, gingival hyperplasia, hepatitis, jaundice and hepatic enzyme elevations, angioedema, erythema multiform, urticaria.
If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
9. DRUG INTERACTIONS:
Amlodipine has been safely administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual glyceryl trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic drugs.
In vitro data from studies with human plasma, indicate that amlodipine has no effect on protein binding of digoxin, phenytoin, warfarin or indomethacin.
Special Studies: Effect of other agents on amlodipine
Cimetidine: Co-administartion of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine.
Grapefruit Juice: Co-administration of 240 ml of grapefruit juice with a single oral dose of amlodipine10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Sildenafil: when amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Special Studies: Effect of amlodipine on other agents
Atorvastatin: Co-administration of multiple 10 mg doss of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady state pharmacokinetic parameters of atorvastatin.
Digoxin: Co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
Warfarin: In healthy male volunteers, the co-administration of amlodipine does not significantly alter the effect of warfarin on prothrombin response time. Co-administration of amlodipine with warfarin did not change the warfarin prothrombin response time.
Cyclosporin: Pharmacokinetic studies with cyclosporine have demonstrated that amlodipine does not significantly alter the pharmacokinetics of cyclosporine.
Drug/Laboratory test interactions: None known
10. PHARMACOLOGICAL PROPERTIES
10.1. Pharmacodynamic Properties
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calsium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which amlodipine relieves angina has not been fully determined but amlodipine reduces total ischaemic burden by the following two actions.
Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal’s or variant angina).
In patients with angina, once daily administration of amlodipine increases total exercise time, time to angina onset, and time to 1 mm ST segment depression, and decreases both angina attack frequency and glyceryl trinitrate tablet consumption.
Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes, and gout.
Use in Patients with Heart Failure: Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II – IV heart failure patients have shown that amlodipine did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection fraction and clinical symptomatology.
A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure receiving digoxin, diuretics and ACE inhibitors has shown that amlodipine did not lead to an increase in risk mortality or combined mortality and morbidity with heart failure.
In a follow-up, long term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure without clinical symptoms or objective findings suggestive or underlying ischaemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total cardiovascular mortality. In this same population amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.
A randomized double-blind morbidity-mortality study called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was performed to compare newer drug therapies: amlodipine 2.5-10 mg/d (calcium channel blocker) or lisinopril 10-40 mg/d (ACE – inhibitor) as first-line therapies to that of the thiazide-diuetic, chlorthalidone 12.5-25 mg/d in mild to moderate hypertension.
A total of 33,357 hypertensive patients aged 55 or older were randomized and followed for a mean of 4.9 years. The patients had at least one additional CHD risk factor, including: previous myocardial infraction or stroke (> 6 months prior to enrollment) or documentation of other atherosclerotic CVD (overall 51.5%), type 2 diabetes (36.1%), HDL-C < 35 mg/dL (11.6%), left ventricular hypertrophy diagnosed by electrocardiogram or echocardiography (20.9%), current cigarette smoking (21.9%).
The primary endpoint was a composite of fatal CHD or non-fatal myocardial infraction. There was no significant difference in the primary endpoint between amlodipine-based therapy and chlorthalidone-based therapy: RR0.98 95% CI (0.90 – 1.07) p=0.65. among Secondary Endpoints, the incidence of heart failure (component of a composite combined cardiovascular endpoint) was significantly higher in the amlodipine group as compared to the chlorthalidone group (10.2% vs 7.7%, RR 1.38, 95% CI [1.25 – 1.52] p<0.001). However, there was no significant difference in all cause mortality between amlodipine-based therapy and chlorthalidone-based therapy. RR 0.96 95% CI [0.89 – 1.02] p=0.20.
In a study involving 268 children aged 6-17 years with predominantly secondary hypertension, comparison of a 2.5 mg dose, and 5.0 mg dose of amlodipine with placebo, showed that both doses reduced Systolic Blood Pressure significantly more than placebo. The difference between the two doss was not statistically significant.
The long-term effects of amlodipine on growth, puberty and general development have not been studies. The long-term efficacy of amlodipine on therapy in childhood to reduce cardiovascular morbidity and mortality in adulthood have also not been established.
10.2. Pharmacokinetic Properties
Absorption, distribution, plasma protein binding: After oral administration of therapeutic doses, amlodipine is well absorbed with is well absorbed with peak blood levels between 6 – 12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 I/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
Biotransformation / elimination: The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.
Use in elderly: The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.
11. OVERDOSE
Available data suggest that gross overdosage could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Administration of activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 10 mg has been shown to significantly decrease amlodipine absorption. Gastric lavage may be worthwhile in some cases. Clinically significant hypotension due to amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be benefitial in reversing the effects of calcium channel blockade. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.
12. SHELF LIFE: 48 months from the date of manufacture.
13. STORAGE: Keep below 25° C, away from light and moisture .
14. HOW SUPPLIED: 03 blisters x 10 film coated tablets/ box.
15. SPECIFICATION: EP
Name and Address of Manufacturer
Remedica Ltd,
Limassol Industrial Estate, Limassol, Cyprus, EU
Name and Address of Registrationer
Nhat Anh Pharmaceutical Co., Ltd.
122/7-9 Dang Van Ngu Str., Ward 14, Phu Nhuan Dist., HCMC, Vietnam
Please read carefully before use.
Further more information please ask your doctor or pharmacist
