Active ingredients: Amlodipine
Norvasc 5 mg and 10 mg tablets
Why is Norvasc used? What is it for?
Norvasc contains the active substance amlodipine which belongs to a group of medicines called calcium channel blockers.
Norvasc is used to treat high blood pressure (hypertension) or a type of chest pain called angina, including a rare form called Prinzmetal's or variant angina.
In hypertensive patients this drug works by relaxing the blood vessels so that the blood can drain more easily. In patients with angina, Norvasc improves the blood supply to the heart muscle which receives more oxygen and thereby prevents chest pain.
This drug does not bring about immediate relief from chest pain due to angina.
Contraindications When Norvasc should not be used
Do not take Norvasc
- If you are allergic (hypersensitive) to amlodipine, or to any of the other ingredients of this medicine listed in section 6, or to any of the other calcium channel blockers. The reaction may be itchy, red skin or difficulty in breathing.
- If you have severe low blood pressure (hypotension)
- If you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition where the heart is unable to supply the body with enough blood).
- If you suffer from heart failure following a heart attack
Precautions for use What you need to know before you take Norvasc
Talk to your doctor or pharmacist before taking Norvasc.
Tell your doctor if you have or have suffered from the following conditions:
- Recent heart attack
- Heart failure
- Severe increase in blood pressure (hypertensive crisis)
- Liver disease (liver disease)
- You are elderly and your dose needs to be increased
Children and adolescents
Norvasc has not been studied in children younger than 6 years of age. Norvasc is only to be used for hypertension in children and adolescents 6 to 17 years of age (see section 3). For further information, consult your doctor.
Interactions Which drugs or foods may change the effect of Norvasc
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Norvasc can affect other medicines, or other medicines can affect Norvasc, such as:
- ketoconazole, itraconazole (antifungal medicines)
- ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV)
- rifampicin, erythromycin, clarithromycin (antibiotics)
- Hypericum perforatum (St. John's wort)
- verapamil, diltiazem (heart medicines)
- dantrolene (infusion for severe body temperature changes)
- simvastatin (cholesterol lowering medicine)
- tacrolimus (medicine used to change the way the immune system works)
- cyclosporine (an immunosuppressant)
Norvasc may lower your blood pressure even more if you are already taking other medicines to treat hypertension at the same time.
Norvasc with food and drink
People taking Norvasc should not drink grapefruit juice as grapefruit and grapefruit juice can cause the levels of the active substance amlodipine to rise in the blood, which may lead to an increase in the blood pressure lowering effect of Norvasc.
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
The safety of amlodipine in pregnant women has not been established. If you think you are pregnant or planning to become pregnant, tell your doctor before taking Norvasc.
Feeding time
It is not known whether amlodipine passes into breast milk. If you are breast-feeding or will start breast-feeding, please tell your doctor before taking Norvasc.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Norvasc may have an effect on the ability to drive or use machines. If the tablets make you feel unwell, dizzy or tired, or cause you a headache, do not drive or operate machinery and contact your doctor immediately.
Norvasc contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, ie it is practically 'sodium-free'.
Dose, Method and Time of Administration How to use Norvasc: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended starting dose is Norvasc 5 mg once daily. The dose can be increased to Norvasc 10 mg once daily.
This medicine can be taken before or after food and drink. You should take this medicine at the same time each day with some water. Do not take Norvasc with grapefruit juice.
Use in children and adolescents
For children and adolescents (6 to 17 years of age), the recommended starting dose is 2.5 mg per day. The maximum recommended daily dose is 5 mg per day. Norvasc 5 mg can be divided into two equal parts to give a dose of 2.5 mg.
It is important to keep taking the tablets for as long as your doctor tells you. See your doctor before you run out of tablets.
Overdose What to do if you have taken too much Norvasc
If you take more Norvasc than you should
If you take too many tablets, your blood pressure may drop too low and this could be a danger. You may feel dizzy, lightheaded, weak or pass out. The drop in blood pressure could be severe enough to shock you. The skin may cool and become clammy and you may lose consciousness. If you have taken too many Norvasc tablets, contact your doctor immediately.
If you forget to take Norvasc
Do not worry. If you forget to take a tablet, skip the missed dose. Take the next tablet at the usual time. Do not take a double dose to make up for a forgotten dose.
If you stop taking Norvasc
Your doctor will tell you how long to take the medicine. Your condition may come back if you stop treatment before your doctor tells you to.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Norvasc
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any of the following side effects, consult your doctor immediately:
- Sudden onset of wheezing, chest pain, shortness of breath or difficulty in breathing
- Swelling of the eyelids, face or lips
- Swelling of the tongue and throat which can cause difficulty in breathing
- Severe skin reactions including intense rash, hives, red skin all over the body, intense itching, blistering, peeling and swelling of the skin, inflammation of the mucous membranes (Stevens Johnson syndrome) or other allergic reactions
- Heart attack, abnormal heart rhythm
- Inflammation of the pancreas which can cause intense abdominal and back pain combined with a feeling of being very unwell
The following very common side effects have been reported. If any of these effects occur or if they persist for more than a week, please contact your doctor.
Very common: may affect more than 1 in 10 people
- Swollen ankles (edema)
The following common side effects have been reported. If any of these effects occur or if they persist for more than a week, please contact your doctor.
Common: may affect up to 1 in 10 people
- Headache, dizziness, somnolence (especially at the start of treatment)
- Palpitations (feel your own heartbeat), redness
- Abdominal pain, nausea
- Altered bowel habits, diarrhea, constipation, indigestion
- Tiredness, weakness
- Visual disturbances, double vision
- Muscle cramps
In addition, the following side effects have been reported. 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.
Uncommon: may affect up to 1 in 100 people
- Mood changes, anxiety, depression, lack of sleep
- Tremor, changes in taste, fainting
- Feeling numb or tingling in the limbs loss of pain sensation
- Ringing in the ears
- Low blood pressure
- Sneezing / runny nose due to inflammation of the lining of the nose (rhinitis)
- Cough
- Dry mouth, vomiting
- Hair loss, increased sweating, itchy skin, red patches on the skin, skin discoloration
- Urinary disorders, need to urinate at night, need to urinate often
- Inability to achieve an "erection; discomfort or enlargement of the breasts in men
- Pain, discomfort
- Joint or muscle pain, back pain
- Weight gain or loss
Rare: may affect up to 1 in 1,000 people
- Confusion
Very rare: may affect up to 1 in 10,000 people
- Low levels of white blood cells and platelets in the blood which can lead to "unusual bruising or a tendency to bleed (damage to red blood cells)
- High blood sugar levels (hyperglycemia)
- A nerve disorder that can cause weakness, tingling or numbness
- Swollen gums
- Bloating (gastritis)
- Abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), increase in liver enzymes which may lead to changes in some medical tests
- Increased muscle tension
- Inflammation of the blood vessels, often with a rash
- Sensitivity to light
- Disorders related to stiffness, tremor and / or movement disorders
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Italian Medicines Agency, website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the "box after 'EXP". The expiry date refers to the last day of that month.
Tablets
Do not store above 25 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Norvasc contains
The active substance in Norvasc 5 mg tablets is amlodipine (as besylate).
The active substance in Norvasc 10 mg tablets is amlodipine (as besylate).
The other ingredients are: anhydrous dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose and sodium starch glycolate.
What Norvasc looks like and contents of the pack
5 mg tablets: White to off-white, octagonal tablets debossed with AML 5 and score line on one side and Pfizer logo on the other side.
10 mg tablets: White to off-white, octagonal tablets debossed with AML-10 on one side and Pfizer logo on the other side.
5 mg tablets: White to off-white, octagonal tablets embossed with AML 5 and score line on one side and white on the other side.
10 mg tablets: White to off-white, octagonal tablets debossed with AML-10 on one side and white on the other side.
Norvasc 5 mg tablets are available in blisters containing 4, 10, 14, 20, 28, 30, 50, 60, 98, 100, 300, 500 tablets and in perforated unit dose blister strips of 50x1 and 500x1 tablets. It is available in blisters containing 4, 10, 14, 20, 28, 30, 50, 60, 90, 98, 100, 300, 500 tablets and in unit dose blister strips 50x1 and 500x1 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
NORVASC TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains amlodipine besylate equivalent to 5 mg amlodipine base.
One tablet contains amlodipine besylate equivalent to 10 mg amlodipine base.
Excipients:
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Tablets.
5 mg tablets: White to off-white, octagonal tablets debossed with AML 5 and score line on one side and Pfizer logo on the other side.
10 mg tablets: White to off-white, octagonal tablets debossed with AML-10 on one side and Pfizer logo on the other side.
The score line is only to make it easier to break and swallow the tablet more easily and not to divide it into equal doses.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hypertension
Stable chronic angina pectoris
Angina following vasospasm (Prinzmetal's angina)
04.2 Posology and method of administration
Dosage
Adults
For both hypertension and angina, the recommended starting dose is 5 mg of Norvasc once a day. This dose can be increased to the maximum dose of 10 mg depending on the individual response.
In hypertensive patients, Norvasc has been used in combination with thiazide diuretics, alpha blockers, beta blockers or angiotensin converting enzyme inhibitors. In patients with angina, Norvasc can be used alone or in combination with other antianginal drugs, in cases of angina refractory to treatment with nitrates and / or beta-blockers at appropriate doses.
No dosage adjustments of Norvasc are required for concomitant administration of thiazide diuretics, beta-blockers or converting enzyme inhibitors.
Special populations
Senior citizens
Norvasc used at similar dosages in elderly and young patients is equally well tolerated. Normally used dosages are recommended in elderly patients, but dose escalation should be considered with caution (see sections 4.4 and 5.2).
Hepatic insufficiency
No specific dosages have been established for patients with mild to moderate hepatic impairment; therefore, the choice of dosage should be made with caution and starting with the lowest dose (see sections 4.4 and 5.2). The pharmacokinetics of amlodipine have not been studied in severe hepatic impairment. In patients with severe hepatic impairment, treatment with amlodipine should be initiated at the lowest dose, followed by gradual dosage adjustment.
Kidney failure
The degree of renal impairment is not related to changes in plasma concentrations of amlodipine, therefore the drug can be used at normal dosages in this category of patients. Amlodipine is not dialysable.
Pediatric population
Children and adolescents with hypertension between the ages of 6 and 17
The recommended oral antihypertensive dose in pediatric patients 6 to 17 years of age is 2.5 mg once daily as a starting dose, which can be increased to 5 mg once daily if the recommended blood pressure values are not achieved after 4 weeks. Doses above 5 mg / day have not been studied in pediatric patients (see sections 5.1 and 5.2).
Doses of amlodipine 2.5 mg cannot be administered with this product.
Children under the age of 6
No data are available.
Method of administration
Tablets for oral administration.
04.3 Contraindications
Amlodipine is contraindicated in patients with:
• hypersensitivity to dihydropyridine derivatives, to amlodipine or to any of the excipients.
• severe hypotension.
• shock (including cardiogenic shock)
• left ventricular outflow obstruction (eg high grade aortic stenosis)
• heart failure with haemodynamic instability after acute myocardial infarction
04.4 Special warnings and appropriate precautions for use
The safety and efficacy of amlodipine during hypertensive crisis have not been evaluated.
Patients with heart failure
Patients with heart failure should be treated with caution. In a long-term, placebo-controlled clinical study in patients with severe heart failure (NYHA class III and IV) amlodipine was associated with more cases of pulmonary edema than placebo (see section 5.1). Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Use in patients with hepatic insufficiency
The plasma half-life of amlodipine is prolonged and AUC values are higher in patients with impaired hepatic function; no specific dosages have been established for these patients. Amlodipine should therefore be initially taken at the lowest dose and used with caution both at the start of treatment and when increasing the dose. Gradual dosage adjustment and careful monitoring may be required in patients with severe hepatic impairment.
Use in elderly patients
In elderly patients, dose escalation should be considered with caution (see sections 4.2 and 5.2).
Use in patients with renal insufficiency
Amlodipine can be used at normal dosages in such patients. The degree of renal impairment is not related to changes in plasma concentrations of amlodipine. Amlodipine is not dialysable.
04.5 Interactions with other medicinal products and other forms of interaction
Effects of other medicinal products on amlodipine
CYP3A4 inhibitors: Concomitant use of amlodipine with potent or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may cause a significant increase in amlodipine exposure. Clinical significance. of these pharmacokinetic changes may be more pronounced in the elderly, therefore clinical monitoring and dosage adjustment may be required.
CYP3A4 inducers: There are no data available regarding the effect of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (eg rifampicin, Hypericum perforatum) may decrease plasma concentrations of amlodipine. Amlodipine should be used with caution when co-administered with CYP3A4 inducers.
Administration of amlodipine with grapefruit or grapefruit juice is not recommended as the bioavailability of amlodipine may increase and consequently potentiate the antihypertensive effect of amlodipine in some patients.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse associated with hyperkalaemia have been observed following intravenous administration of verapamil and dantrolene. Due to the risk of hyperkalaemia, it is recommended to avoid concomitant administration of calcium channel blockers such as amlodipine in patients prone to malignant hyperthermia and in the treatment of malignant hyperthermia.
Effects of amlodipine on other medicinal products
The effects of amlodipine on the decrease in blood pressure add to the effects of the decrease in pressure exerted by other antihypertensive agents.
In clinical interaction studies, amlodipine did not alter the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine.
04.6 Pregnancy and lactation
Pregnancy
The safety of amlodipine during pregnancy has not been established.
In animal studies, reproductive toxicity effects were observed following administration of high doses (see section 5.3).
Use in pregnancy is only recommended if there is no safer alternative and when the disorder carries major risks for the mother and fetus.
Feeding time
It is not known whether amlodipine is excreted in human milk. The decision to continue / discontinue breastfeeding or to continue / discontinue amlodipine therapy must be considered taking into account the benefits of breastfeeding for the infant and the benefits of therapy with amlodipine for the mother.
Fertility
Reversible biochemical changes in the head of spermatozoa have been reported in patients treated with calcium channel blockers. There are insufficient clinical data on the potential effect of amlodipine on fertility. In a rat study, undesirable effects on male fertility were reported (see section 5.3).
04.7 Effects on ability to drive and use machines
Amlodipine has mild or moderate effects on the ability to drive or use machines. If patients taking amlodipine suffer from dizziness, headache, fatigue or nausea, their ability to react may be impaired. Caution is recommended especially at the start of treatment.
04.8 Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions during amlodipine treatment were somnolence, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle swelling, edema and fatigue.
Tabular summary of adverse reactions
The following adverse reactions have been observed and reported during treatment with amlodipine with the following frequencies: very common (≥1 / 10); common (≥1 / 100 y
Within each frequency class, undesirable effects are reported in descending order of severity.
* in most cases due to cholestasis
Exceptional cases of extrapyramidal syndrome have been reported.
04.9 Overdose
Human experience with intentional overdose is limited.
Symptoms
Available data suggest that severe peripheral vasodilation and possible reflex tachycardia may occur following overdose. Marked and possibly prolonged systemic hypotension has been reported up to and including cases of shock with a fatal outcome.
Treatment
Clinically significant hypotension due to amlodipine overdose requires active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of the lower limbs, and attention to circulating fluid volume and diuresis.
For the restoration of vascular tone and arterial pressure, a vasoconstrictor can help, if there are no contraindications for its use. Intravenous administration of calcium gluconate may prove useful in neutralizing the effects of calcium channel blocking.
Gastric lavage can be helpful in some cases. Administration of charcoal to healthy volunteers, either immediately or within two hours of taking 10 mg amlodipine, has been shown to significantly reduce the absorption of amlodipine.
Since amlodipine is largely protein bound, dialysis is unlikely to be useful.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: calcium channel blockers, selective calcium channel blockers with predominantly vascular effect.
ATC code: C08CA01.
Amlodipine is an inhibitor of the influx of calcium ions belonging to the group of dihydropyridines (blockers active on slow channels or antagonists of calcium ions) and inhibits the flow of calcium ions through the membrane of myocardiocytes and vascular smooth muscle cells.
The antihypertensive action of amlodipine is due to the direct relaxation of the vascular smooth muscle. The exact mechanism of action that determines the antianginal effect of amlodipine is not yet fully known, but amlodipine reduces the total ischemic load based on the following two actions :
1) Amlodipine dilates the peripheral arterioles thus reducing the total peripheral resistance (afterload) against which the heart works. As the heart rate remains stable, this reduction in cardiac work results in a decrease in oxygen demand and energy consumption by the myocardium.
2) The mechanism of action of amlodipine probably also determines the dilation of the main coronary arteries and coronary arterioles, both in the normally perfused and in the ischemic regions. This dilation increases the oxygen supply to the myocardium in patients with coronary artery spasm (Prinzmetal's or variant angina).
In hypertensive patients, a single daily dose causes a clinically significant reduction in blood pressure, both in supine and standing position, still evident 24 hours after administration. Due to the gradual onset of the effect of amlodipine, acute hypotension is not a drug related event.
In patients with angina, a single daily administration of amlodipine increases total exercise time, time to onset of an anginal attack, time to onset of 1 mm ST segment elevation, and decreases anginal attack frequency and consumption. of nitroglycerin.
Treatment with amlodipine is not associated with any undesirable metabolic effects or alterations in the plasma lipid profile; amlodipine is suitable for use in patients suffering from concomitant diseases such as asthma, diabetes and gout.
Use in patients with coronary artery disease (CAD)
The efficacy of amlodipine in the prevention of clinical events in patients with coronary artery disease (CAD) was evaluated in an independent, multicenter, randomized, double-blind, placebo-controlled clinical study in 1997 patients: the CAMELOT study (Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis - Comparison between amlodipine and enalapril in reducing thrombotic events). Of these patients, 663 were treated with amlodipine 5-10 mg, 673 patients were treated with enalapril 10-20 mg, and 655 patients were treated with placebo, in addition to standard treatment with statins, beta-blockers, diuretics and aspirin. , for 2 years. The main efficacy results are shown in Table 1. These results indicate that amlodipine treatment was associated with fewer hospitalizations for angina and revascularization procedures in patients with coronary artery disease.
Use in patients with heart failure
S.Hemodynamic studies and controlled clinical trials on exercise tolerance in patients with NYHA class II-IV heart failure have shown that Norvasc does not aggravate their clinical condition with regard to exercise tolerance, left ventricular ejection fraction and symptoms. clinic.
A placebo-controlled clinical trial (PRAISE), designed to evaluate patients with heart failure NYHA class III-IV receiving digoxin, diuretics and ACE inhibitors, showed that Norvasc does not increase the risk of mortality or the risk of mortality and morbidity. considered jointly, in patients with heart failure.
In a long-term, placebo-controlled follow-up study (PRAISE-2) conducted in patients with NYHA class III and IV heart failure, treated with Norvasc, with no clinical symptoms or objective findings suggesting disease Ischemic, in therapy with fixed doses of ACE inhibitors, digitalis and diuretics, the use of Norvasc had no effect on total cardiovascular mortality. In the same population, Norvasc was associated with an increase in cases of pulmonary edema.
Heart Attack Prevention Treatment Clinical Study (ALLHAT)
A double-blind randomized morbidity-mortality trial called ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was conducted to compare the two most recent drug therapies: amlodipine 2.5-10 mg / day ( calcium channel blocker) or lisinopril 10-40 mg / day (ACE inhibitor) as first-line therapies compared to treatment with the thiazide diuretic chlorthalidone 12.5-25 mg / day, in mild to moderate hypertension.
A total of 33,357 hypertensive patients ≥ 55 years of age were randomized and followed for a mean of 4.9 years. Patients had at least one additional risk factor for heart failure, including: previous myocardial infarction or stroke (> 6 months prior to enrollment) or other documented atherosclerotic cardiovascular disease (overall 51.5%), type 2 diabetes (36 , 1%), C-HDL hypertrophy of the left ventricle diagnosed by electrocardiogram or echocardiography (20.9%), currently smoker (21.9%).
L"endpoint primary consisted of a combination of fatal coronary heart disease or non-fatal myocardial infarction. There was no significant difference in "endpoint primary between amlodipine and chlorthalidone therapy: RR 0.98, 95% CI (0.90-1.07) p = 0.65. Among endpoint secondary, the incidence of heart failure (one of the components ofendpoint cardiovascular composite) was significantly higher in the amlodipine group than in the chlorthalidone group (10.2% vs 7.7%, RR: 1.38, 95% CI [1.25-1.52] p
Pediatric use (children ≥ 6 years of age)
In a study of 268 children aged 6 to 17 years mainly with secondary hypertension, in which amlodipine 2.5 mg and 5.0 mg were compared with placebo, both doses of the drug were shown to reduce systolic blood pressure to a significantly greater extent than placebo. The difference between the two dosages was not statistically significant.
The long-term effects of amlodipine on growth, puberty and general development have not been studied. Furthermore, the long-term efficacy of pediatric amlodipine therapy in reducing cardiovascular morbidity and mortality in adulthood has not been established.
05.2 Pharmacokinetic properties
Absorption, distribution, binding to plasma proteins: After oral administration of therapeutic doses, amlodipine is absorbed gradually, with peak plasma levels within 6-12 hours of administration. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 L / kg. Studies in vitro showed that amlodipine is approximately 97.5% bound to plasma proteins.
Food intake does not alter the bioavailability of amlodipine.
Biotransformation / elimination
The terminal plasma elimination half-life is approximately 35-50 hours, which justifies once-daily administration. Amlodipine is extensively metabolised by the liver to inactive compounds and 10% is eliminated in the urine as the base molecule and 60% in the metabolised form. .
Use in hepatic insufficiency
Very limited clinical data are available regarding the administration of amlodipine in patients with hepatic insufficiency. Patients with hepatic insufficiency have a lower clearance of amlodipine resulting in a longer half-life and an increase in AUC of approximately 40-60%.
Use in the elderly
The time to reach peak plasma concentrations of amlodipine in elderly and younger subjects is similar. In elderly patients the clearance of amlodipine tends to decrease causing increases in the AUC and elimination half-life of the drug. Increases in AUC and elimination half-life comparable to those predicted for this patient population were observed in heart failure patients.
Use in pediatric age:
A pharmacokinetic study was conducted in a population of 74 hypertensive children aged 1 to 17 years (including 34 patients aged 6 to 12 years and 28 patients aged 13 to 17 years). administered amlodipine at a dosage between 1.25 and 20 mg, once or twice daily. In children between the ages of 6 and 12 and in adolescents between 13 and 17 years of age, the clearance typical oral (CL / F) was 22.5 and 27.4 L / hr in males and 16.4 and 21.3 L / hr in females, respectively. A "wide variability" in exposure was observed between individuals. Data on children under the age of 6 are limited.
05.3 Preclinical safety data
Reproductive toxicology:
Reproduction studies in rats and mice have shown delayed parturition, prolonged labor and reduced neonatal survival at doses approximately 50 times the maximum recommended human dose based on the mg / kg ratio.
Reduction of fertility
There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females for 14 days before mating) at doses up to 10 mg / kg / day (equivalent to 8 times the maximum dose of 10 mg on a recommended mg / m2 basis in humans *). Another study conducted in male rats treated with amlodipine besylate for 30 days at a dose comparable to that administered to humans (mg / kg), showed a decrease in testosterone and follicle-stimulating hormones in plasma, as well as decreases in density. sperm and the number of mature sperm cells and Sertoli cells.
Carcinogenesis, Mutagenesis
Rats and mice treated for two years with dietary amlodipine, at concentrations calculated to provide daily levels of 0.5, 1.25 and 2.5 mg / kg / day, showed no evidence of carcinogenicity. The highest dose (for rats equal to twice the maximum clinical dose of 10 mg on a mg / m2 basis recommended in humans * and for mice similar to this maximum recommended dose) was close to the maximum tolerated dose by mice but not from rats.
Mutagenicity studies did not reveal any drug-related effects on either the genetic or chromosomal level.
* Calculated on a patient weighing 50 kg
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
5 mg and 10 mg tablets
Microcrystalline cellulose,
anhydrous dibasic calcium phosphate,
sodium starch glycolate,
magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 mg and 10 mg tablets
4 years
06.4 Special precautions for storage
5 mg and 10 mg tablets
Store at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
5 mg tablets
PVC-PVDC / Al blisters containing 4, 10, 14, 20, 28, 30, 50, 60, 98, 100, 300, 500 tablets
PVC-PVDC / Al blisters in calendar packs containing 28 and 98 tablets
PVC-PVDC / Al divisible unit dose blisters containing 50x1 and 500x1 tablets
10 mg tablets
PVC-PVDC / Al blisters containing 4, 10, 14, 20, 28, 30, 50, 60, 90, 98, 100, 300, 500 tablets
PVC-PVDC / Al blisters in calendar packs containing 28 and 98 tablets
PVC-PVDC / Al divisible unit dose blisters containing 50x1 and 500x1 tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
NORVASC 5 mg tablets: AIC n. 027428010
NORVASC 10 mg tablets: AIC n. 027428022
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
7 October 2011
