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Cordarone Tablet

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Cordarone Tablet
Cordarone® 200 mg
Amiodarone

QUALITATIVE AND QUANTITATIVE COMPOSITION:
Each tablet content :
Amiodarone (NN) hydrochlorida ........................................ 200 mg
Excipient: include lactose

PHARMACEUTICAL FORM
Tablet of 200 mg Amiodarone

PHARMACOLOGICAL PROPERTIES
Anti arrhythmic properties:
  • Reduced sinus automaticity leading to bradycardia unresponsive to atropine administration.
  • Non competitive alpha and beta adrenergic inhibition.
  • Slowing in sino-atrial, atrial and nodal conduction, which is increased in proportion to rhythm rapidity
  • No change in intra ventricular conduction.
  • Increased in refractory period and decrease of myocardial oxcitability at the atrial, nodal and ventricular levels.
  • Slowing in conduction and prolongation of refractory periods. in accessory atrioventricular pathways.

Other properties:
  • Moderate drop in peripheral resistance and decrease in heart rate leading to a reduction of oxygen intake.
  • Increase of coronary output due to a direct effect on myocardial arteries smooth muscle.
  • Maintenance of cardiac output due to a decrease in aortic pressure and peripheral resistance.

Others
  • No significant negative inotropic effect.

PHARMACOKINETIC PROPERTIES
Amiodarone has a slow transit and a high affinity to tissues.
Oral bioavailability has varied between 30 and 80% along with individual patients (mean value around 50%). Following single administration, peak plasma concentrations are reached after 3 to 7 hours. Therapeutic effects are usually obtained after one week (from a few days to two weeks), according to the loading dose.
Amiodarone has a long half-life including considerable inter-patient variability (from 20 to 100 days). During the fir days of therapy, the drug accumulates in almost all tissues, especially the adipose tissue.
Elimination occurs after a few days and steady-state plasma concentration is reached between 1 to several months depending on each individual patient. Due to the above characteristics, loading doses should be used in order to rapidly obtain the impregnation of tissues that is necessary to have a therapeutic effect.
Iodine is partly removed from the molecule and is found in urine as Iodure; this corresponds to 6mg/24 hours when 200mg of amiodarone is given daily. The remaining part of the molecule, thus including most of iodine, is eliminated in the faces following hepatic excretion.
The negligible renal excretion allows the administration or usual doses in patients with renal failure.
Following treatment discontinuation, the elimination continues ever several months; the persistence or a residual effect over 10 days to one month should be taken into account.

CLINICAL PARTICULARS
Therapeutic Indications
Cordarone® is indicated only for the treatment of severe rhythm disorders, not responding to other therapy or when other treatment cannot be used:
  • Atrial rhythm disorders (conversion of fibrillation or flutter, and maintenance of sinus rhythm following conversion).
  • Modal rhythm disorders
  • Ventricular rhythm disorders (life-threatening ventricular tachycardia solves, prevention of ventricular tachycardia attacks or ventricular fibrillation episodes. 
  • Rhythm disorders associated with Wolf-Parkinson-While syndrome.
In view of its pharmaceutical properties, amiodarone is indicated in the above rhythm disorders especially when they are associated with an underlying heart disease (coronary insufficiency, heart failure).

DOSAGE AND ADMINISTRATION
Initial stabilization: usual dosage is 600mg daily and may be continued for 8 to 10 days.
Maintenance: The minimum effective dosage should be used; according to individual response, It may. range between 100mg daily to 400mg daily. Cordarone® may be given on alternate (200 mg may be given every other day where 100mg are recommended daily);

CONTRA INDICATlONS
This medicine is contraindicated in the following situations:
  • Sinus bradycardia and sino-atrial block not corrected by a pacemaker;
  • Sinus disease not corrected by a pacemaker (risk of sinus arrest) .
  • High-degree conduction disorders not corrected by a pacemaker;
  • Hyperthyroidism due to its possible exacerbation by amiodarone;
  • Known hypersensitivity to iodine or amiodarone;
  • The last 6 months of pregnancy;
  • Breast-feeding
  • Combination with medicines that can induce torsades de pointes:
    • class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide, etc).
    • class III antiarrhythmics (sotalol, dofetillide, ibutilide etc),
    • sultopride,
  • other medicines, such as bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, sparfloxacin, etc. (cf. Interactions with other medicinal products and other forms of interaction).
This medicine IS NOT GENERALLY RECOMMENDED in combination with:
  • injectable diltiazem,
  • halofantrine, pentamidine, moxifloxacine,
  • certain neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, amisulpride, tiapride primozide, haloperidol, droperidol),
  • and with beta-blockers other than sotalol and esmolol (cf. Interactions with other medicinal products and other forms of interaction).

SPECIAL WARNING
Warnings
An ECG must be performed before starting treatment.
  • Slowing of heart rate may be accentuated in elderly patients.
  • The electrocardiogram is modified under amiodarone. This "cordaronic" modification consists of a prolongation in QT reflecting a repolarisation prolongation, possibly with the appearance of a U wave; this is a sign of therapeutic impregnation and not of toxicity.
  • The onset of 2nd or 3rd-degree atrioventricular block, sino-atrial block or bifascicular block should lead to suspension of treatment. 1st-degree atrioventricular block should lead to increased monitoring.
  • The presence of iodine in the medicinal product falsifies certain thyroid tests (binding of radioactive iodine, PBI); however, thyroid function assessment is still possible (T3, T4, TSHus).
  • Combination (cf. Interactions ,with other medicinal products and other forms of interaction) with:
    • beta-blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions for use).
    • Verapamil and diltiazem, should only be considered in the prevention of life-threatening ventricular arrhythmias.
Due to the presence of lactose, this medicinal product is contraindicated in the event of congenital galactosaemia, glucose and galactose malabsorption syndrome or lactase deficiency.
The onset of dyspnoea or a dry cough, alone or associated with a deterioration in general condition, should suggest the possibility of pulmonary toxicity and requires X-ray (Cf. Undesirable effects).

PRECAUTION
Precautions for use
Electrolyte balance disturbance and, in particular, hypokalaemia: it is important to take into account situations that may be associated with hypokalaemia since the latter can promote. the onset of proarrhythmic effects.
Hypokalaemia should be corrected prior to administration of amiodarone.
The undesirable effects mentioned below are usually related to excessive drug levels; they can be avoided or their severity minimized by carefully seeking the minimum maintenance dosage.
Patients should be advised to avoid exposure to sun or to use sun protection during treatment.
Amiodarone can cause thyroid anomalies (d Undesirable effects).
Assay of TSH is recommended in all patients before treatment and then regularly throughout treatment - for example, every 6 months - and several months after its withdrawal.
TSH levels should be measured in the event of clinical suspicion of dysthyroidism (cf. Undesirable effects).
In children, the safety and efficacy of amiodarone have not been evaluated by controlled clinical trials.
Regular monitoring of liver function (transaminase levels) is useful to screen for liver damage caused by amiodarone (cf. Undesirable effects).

Anaesthesia
Before surgery, the anaesthetist must be informed that the patient is treated with amiodarone.
Chronic treatment with amiodarone may lead to exacerbation, in terms of undesirable effects, of the haemodynamic risks of general or local anaesthetics.
These concern, in particular, bradycardiac and hypotensive effects, reduced cardiac output and conduction disturbances.
In addition, a few cases of acute respiratory distress have been observed immediately after surgery in patients treated with amiodarone. Consequently, close monitoring is recommended during artificial ventilation of such patients (Cf. Undesirable effects).

DRUG INTERACTIONS
A number of antiarrhythmics drugs depress cardiac automatism, conduction and contractility.
The combination of antiarrhythmics from different classes can provide a beneficial therapeutic effect, but is usually VERY DELICATE, requiring close clinical and ECG monitoring. The combination of antiarrhythmics inducing torsades de pointes (such as amiodarone) is CONTRAINDICATED.
The combination of antiarrhythmics from the same class is NOT RECOMMENDED. apart from in exceptional cases, due to the increased risk of cardiac undesirable effects. Combination with medicines with negative inotropic, bradycardiac and/or atrioventricular conduction slowing drugs is DELICATE and requires close clinical and ECG monitoring.

Contraindicated combinations
-Medicinal products that can induce torsades de pointes:
-Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide),
-Class III antiarrhythmics (dofetilide, ibutilide, sotalol),
-Other medicinal products, such as: bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, vincamine IV,
-Sultopride, Increased risk of ventricular arrhythmia and in particular, torsades de pointes.
+Sparfloxacin, Risk of torsades de pointes due to a prolongation in QT interval (addition of electrophysiological effects).

Inadvisable combinations
+Neuroleptics inducing torsade de pointes:
Some phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamide neuroleptics (amisulpride, sulpiride, tiapride), butyrophenone neuroleptics (droperidol, haloperidol), other neuroleptics (pimozide). Increased risk of ventricular arrhythmia and, in particular, torsades de pointes.
+Halofantrine, moxifloxacine, pentamidine
Increased risk of ventricular arrhythmia and, in particular, torsades de pointes. If possible, suspend the non-antibiotic torsadogenic drug. If the combination cannot be avoided, prior control of QT and constant electrocardiographic monitoring.
+Injectable diltiazem
Risk of bradycardia and atrioventricular block. If this combination cannot be avoided, only administer under close clinical and constant electrocardiographic monitoring.
+Beta-blockers (other than sotalol and esmolol)
Contractility, automatism and conduction disturbances (suppression of compensatory sympathic mechanisms).

Combinations requiring precautions for use
+Oral anticoagulants
Increased anticoagulant effect and haemorrhagic risk.
More frequent control of prothrombin rate and monitoring of INR. Adjustment of oral anticoagulant dosage during treatment with amiodarone and after its withdrawal.
+Ciclosporin
Increase in circulating levels of ciclosporin due to a reduction in its hepatic metabolism with a risk of nephrotoxic effects.
Assay of blood ciclosporin concentrations, monitoring of kidney function and adjustment of dosage during combination with amiodarone and after its withdrawal.
+Oral diltiazem
Risk of bradycardia or atrioventricular block, particularly in the elderly. Clinical and electrocardiographic monitoring.
+Digitalis drugs
Depression of automatism (excessive bradycardia) and atrioventricular conduction disturbances. In the event of use of digoxin, Increased blood digoxin levels due to reduced digoxin clearance.
Clinical and electrocardiographic monitoring and, if necessary monitoring of blood digoxin levels and adjustment of digoxin dosage.
+Esmolol
Contractility, automatism and conduction disturbances (suppression of compensatory sympathic mechanisms).
Clinical and electrocardiographic monitoring.
+Potassium-lowering drugs: potassium-lowering diuretics (alone or in combination), stimulant laxatives, glucocorticoids (systemic route), tetracosactide, amphotericin B (IV route).
Increased risk of ventricular arrhythmia and, in particular, torsades de pointes (hypokalaemia is a predisposing factor).
Clinical, laboratory and electrocardiographic monitoring.
+Phenytoin
Increase in plasma concentrations of phenytoin with signs of overdose and, in particular, neurological signs (reduced hepatic metabolism of phenytoin).
Clinical monitoring, control of plasma concentrations of phenytoin and, if necessary, adjustment of the latter's dosage.
+Bradycardiac drugs: bradycardiac calcium antagonists. (diltiazem, verapamil), beta-blockers (except sotalol), clonidine; guanfacine, digitalis drugs mefloquine; anticholinesterase drugs (donezepil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine).
Increased risk of ventricular arrhythmia and, in particular, torsades de pointes. Clinical and electrocardiographic monitoring.
+Simvastatin
Increased risk of undesirable effects (dose-dependent), such as rhabdomyolysis (reduced hepatic metabolism of the cholesterol-lowering drug).
Do not exceed a dosage of 20 mg/d simvastatin.
If the therapeutic goal is not achieved at this dosage, use another statin not concerned by this type of interaction.

PREGNANCY AND LACTATIONS
Pregnancy
Animal studies have not revealed any teratogenic effect. In the absence of any teratogenic effect in animals no malformative effect is expected in humans.
In fact, to date, substances 'responsible for malformations in humans have been revealed to be teratogenic in animals in the course of properly conducted studies in both species.
Clinically, no sufficiently relevant data are currently available to be able to assess a potential malformative effect of amiodarone when It IS administered during the first three months of pregnancy.
Since the foetal thyroid begins to blind iodine from 14 weeks after the last menstrual period, no effects on the foetal thyroid are expected in the event of administration prior to this.
Iodine overload related to the use of this medicine after this time can lead to foetal hypothyroidism, which may be biological or even clinical (goitre).
Consequently, the use of this medicine is contraindicated after the first 3 months of pregnancy.

Lactation
Amiodarone and its metabolite, along with iodine, cross into breast milk at concentrations greater than those in maternal plasma. Due to the risk of hypothyroidism In the newborn infant, breast-feeding is contraindicated in the event of treatment with this medicine.

EFFECT ON ABILITY TO DRIVE AND USE MACHINES
Not relevant

UNDESIRABLE EFFECTS
Ocular signs
Corneal micro-deposits, which are almost constant In adults, usually remain localized to the area under the pupil and do not contraindicate continuation of treatment. In exceptional cases these may be accompanied by perception of colored halos in dazzling light or sensations of mistiness.
Composed of complex lipid deposits, corneal micro-deposits are always entirely reversible on discontinuation of treatment.
A few cases of optic neuropathy (optic neuritis) with blurred vision, reduced vision and papillary oedema at the fundus of the eye have been reported. The outcome may be a more or less severe reduction in visual acuity. The relationship with amiodarone does not appear to have been established at the current time. However in the event of any other obvious cause, it is recommended that treatment be suspended.

Cutaneous signs
Photosensitisation. Subjects are advised to avoid exposure to sun (and ultraviolet rays in general) during treatment.
Cases of erythema have also been reported during radiotherapy.
Cases of skin rashes - generally not very specific - and a few cases of exfoliative dermatitis have been reported, without the relationship with the medicine having been clearly established.
Exceptional cases of lilac or slate-grey colored pigmentation of the skin may occur at high daily dosages prescribed for a long period of time; after treatment withdrawal, this pigmentation is slow to disappear (10 to 24 months).

Thyroid signs
In the absence of any clinical signs of dysthyroidism, a "dissociated" thyroid hormone level (increase in T4, T3 normal or slightly reduced) does not warrant withdrawal of treatment.
Hypothyroidism has a classic form: weight gain, apathy, drowsiness and clear elevation in TSH signal its diagnosis. Withdrawal of the treatment leads to a gradual return to normal thyroid function within a period of 1 to 3 months; this withdrawal is not essential. If the indication so warrants, amiodarone may be continued, combining it with L-thyroxine-based substitutive opotherapy, with TSH levels acting as a guide for the dosage.
Hyperthyroidism is more misleading: with few symptoms (slight unexplained weight loss, reduction in anti-angina and/or antiarrhythmic efficacy); psychiatric forms in the elderly, or even thyrotoxicosis. A reduction in ultra-sensitive TSH levels confirms the diagnosis.
It is essential to suspend amiodarone: this is usually enough to trigger clinical recovery within a period of 3 to 4 weeks; Severe cases can lead to the patient's death making it necessary to urgently instigate appropriate treatment. If. the thyrotoxicosis is worrying, either in itself or due to its effects on the precarious myocardial balance, the inconstant efficacy of synthetic anti-thyroid drugs leads to straightforward corticosteroid therapy (1 mg/kg) being recommended, for a sufficiently long period of time (3 months).
Cases of hyperthyroidism have been reported as long as several months following discontinuation of amiodarone.

Pulmonary signs
Cases of diffuse interstitial or alveolar pneumopathy and bronchiolitis obliterans organizing pneumonia (BOOP) have been reported. The onset of effort dyspnoea either isolated or associated with a deterioration In general condition (fatigue, weight loss, febricula) - requires radiological control and, if necessary, suspension of treatment. These types of pneumopathy can actually develop into pulmonary fibrosis.
Early withdrawal of amiodarone-associated or not with corticosteroid therapy leads to a regression in the disturbances. Clinical signs usually disappear in 3 or 4 weeks. Radiological and function improvement is usually slower (several months).
A few cases of pleurisy, generally associated with interstitial pneumopathies, have been reported.
A few cases of bronchospasm have been reported, particularly in asthmatic patients.
A few cases of acute respiratory distress syndrome, sometimes fatal, have been observed, sometimes immediately following surgery (a possible interaction with high doses of oxygen has been suggested) (cf. Special warnings and special precautions for use).

Neurological effects
These are rare:
  • The prolonged administration of amiodarone can cause sensory, motor or mixed peripheral neurophaties and myopathies. These may occur after Just a few months of treatment but sometimes after several years. They are generally reversible on treatment withdrawal. However, this recovery may be incomplete, very slow and occur only several months after treatment discontinuation.
  • Other disturbances reported: tremor or other extra-pyramidal symptoms, cerebellar-type ataxia, exceptional benign intra-cranial hypertension, sleep disturbances including nightmares.

Hepatic signs
Cases of liver disease have been reported; these cases have been diagnosed by an elevation in serum transaminase levels. In fact, the following have been reported:
  • Isolated and generally moderate (1.5 to 3 times normal values) elevation in transaminase levels, regressing following a reduction in the dosage or even spontaneously.
  • Exceptionally (a few isolated cases), acute liver disease with hypertransaminasaemia and/or jaundice, sometimes fatal, requiring suspension of treatment.
  • Rare cases of chronic liver disease during prolonged treatment. The histology is that of pseudo-alcoholic hepatitis. The discretion of the clinical and laboratory picture (inconstant hepatomegaly, hypertransaminasaernia between 1.5 and 5 times normal levels) warrants regular monitoring of liver function. Hypertransaminasaemia - even moderate-occurring after treatment for more than 6 months may suggest a diagnosis of chronic liver disease. The clinical and laboratory disturbances usually regress after treatment is withdrawn. A few cases of an irreversible outcome have been reported.

Cardiac effects
Generally moderate, dose-dependent bradycardia. In certain cases (sinus dysfunction, elderly patients), marked bradycardia and, more exceptionally, sinus arrest have been reported.
Rarely: conduction disturbances (sino-atrial block, atrioventricular block of varying degrees).
The arrythmogenic effect of amiodarone is weak, less than that of most antiarrhythmic drugs and generally occurs in some drug combinations (cf. Interaction with other medicinal products and other forms of interaction) or electrolyte balance disturbances.


Miscellaneous effects
  • Benign gastrointestinal disturbances (nausea, vomiting, dysgeusia), usually occurring during initial treatment and disappearing when the dosage is reduced. A few cases of epididymitis have been reported. The relationship with the medicine does not appear to have been established. A few rare cases of alopecia have been observed.
  • A few isolated cases, expressed in a variety of ways, have been observed in a context suggesting a hypersensitivity reaction: vascularitis, renal impairment with a moderate elevation in creatinine, thrombopaenia.

OVER DOSAGE
There is little documentation available on the acute administration of high doses of amiodarone. A few cases of sinus bradycardia, ventricular arrhythmia - in particular, torsades de pointes - and liver damage have been reported. Treatment should be symptomatic. Given the kinetics of the product, monitoring for a sufficiently long period of time - particularly cardiac monitoring - is recommended.
Amiodarone and its metabolites cannot be dialysed.

Do not use later than the date of expiry date

SPECIAL PRECAUTIONS FOR STORAGE
Store at temperature below 30°C.

Harus Dengan Resep dokter

Reg.No.DKI8977400410A1

Pack size: Box of 3 blisters of 10 tablets

SANOFI-AVENTIS FRANCE
1-13 boulevard Romain Rolland
75014 PARIS - FRANCE

Manufacture by :
Sanofi Winthrop Industrie
1, rue de la Vierge - Ambares et Lagrave
33565 Carbon Blanc Cedex - France

Imported By
PT. sanofi-aventis Indonesia
Jakarta - INDONESIA

Isordil

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Isordil
Isordil*
(Isosorbide Dinitrate)

DESCRIPTlON
Isordil is a white, crystalline odorless compound. It is sparingly soluble in water and freely soluble in alcohol. The chemical name for isosorbide dinitrate is 1, 4, 3, 6 - dianhydro-sorbitol-2, 5- dinitrate.

CLINICAL PHARMACOLOGY
The exact mechanism of action of the nitrates in the relief of angina pectoris is not fully understood. They appear to relieve classic angina pectoris by reducing myocardial oxygen demand, i. e. by decreasing the heart's "afterload" and "preload: through dilatation of peripheral venous capacitance and, to a lesser extent, arteriolar resistance vessels Nitrates my cause a redistribution of coronary blood flow to ischemic areas by selectively dilating large coronary vessels or collateral vessels which may develop secondary to myocardial ischemia. After therapeutic doses of the drug, systemic arterial pressure is usually decreased: heart rate is unchanged or undergoes a slight compensatory increase. In the absence of heart failure. cardiac output transiently increases and then decreased. Pulmonary vascular resistance. and pulmonary pressure are decreased. The antianginal effects of sub-lingual Isordin generally occur within 2 - 5 minutes after administration and last for 1 - 2 hour. The hemodynamic effects of the oral tablets are observed within 20-60 minutes and last for 4-6 hours
Pharmacokinetics. Gastrointestinal absorption of Isordil tablets is rapid and complete, The drug undergoes an extensive first pass effects with some inter patient variation Isordil is metabolized to two monotritrates which subsequently undergo glucuronidation.
Less than 1 % of Isordil bound to plasma proteins, plasma concentrations of Isordil and mononitrates were compared after administrations of sublingual (2 x 5 mg) and oral (2 x 10 mg) tablets to volunteers. The sublingual dosage form was more rapidly absorbed than the oral formulation as evidenced by the earlier peak concentrations of the parent drug and the mononitrates The half-life of the parent drug was 0.2 and 0.5 hours for the sublingual and oral tablets respectively.
For 2-Isosorbide mononitrates the half-life was 20 hours for bath dosage forms. For 5- isosorbide mononitrates.the half-life of the sublingual tablets was 5.8 hours while that of the oral tablets was 4.5 hours. With chronic administration significant plasma accumulation of the parent compound occurs, presumably the result of saturation of the intrahepatic biotransformation process.
The elimination phase after bath acute and chronic administration of Isordil appears to be at least
biexponential. Essentially all of the drug is eliminated by the kidneys. principally as isosorbide glucuronide.

INDICATIONS
Angina Pectoris

Isordil Oral Tablets: For the prophylaxis of angina pectoris Isordil may reduce the frequency, duration and severity of anginal attacks. Exercise tolerance may be improved and the need for nitroglycerin may be reduced
The oral tablets are not indicated for acute prophylaxis of an anginal attack

Isordil Sublingual Tablets: For treatment of angina pectoris and for prophylaxis in situations likely to provoke an anginal attack

Congestive Cardiac failure
Acute and chronic congestive cardiac failure (including that associated with myocardial infarction). Based on current knowledge, Isordil should be considered only as adjunct to the more conventional modes of therapy (cardiac glycosides and diuretics)

CONTRAINDICATlONS
Hypersensitivity or idiosyncrasy to Isordil or related compounds.
Cardiogenic shock, marked hypotension and circulatory collapse.

WARNINGS AND PRECAUTIONS
Severe hypotensive response, particulary with upright posture. may occur with even small doses of Isordil. Paradoxical bradycardia and increased angina pectoris may accompany nitrate-induced hypotension. The drug should be used with caution in subjects who may have blood volume depletion from diuretic therapy or in subjects who have low systolic blood pressure (e.g. below 90 mm Hg)
In the treatment of acute or chronic cardiac failure, pulmonary capillary pressure should not be allowed to fall below 15 mm Hg or systolic blood pressure below the physiological range in normal or hypertensive patients Systolic pressure should be preserved in patients with pre-existing hypotension in the range of 90-100 mm Hg
As with other vasodilators, isordil may cause paradoxical side effects in sensitive patients, which may increase ischemia and may even lead to extension of myocardial damage and advanced congestive heart failure. if one elects to use organic nitrates in the early infarctions hemodynamic monitoring and frequent clinical assessment should be used because of the potential deleterious effects of hypotension
Marked symptomatic, orthostatic hypotension have been reported when calcium channel blockers and organic nitrates were used in combination
Dose adjustment of either class of agents may be necessary.
Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy
Tolerance of this drug and cross tolerance to other nitrates and nitrites may occur. The importance of tolerance to the appropriate use of isordil in the management of patients with angina pectoris has not been determined
In clinical trials in angina patients, there are reports of anginai attacks being more easily provoked and of rebound in the hemodynamic effects soon after nitrate withdrawal. It seems prudent, therefore, to gradually withdraw patients from isosorbide dinitrate when the therapy is being terminated, rather than stopping the drug abruptly
Carcinogenesis, Mutagenesis, Impairment of Fertility - No long term studies in animals have been performed to evaluate the carcinogenic potential of this drug. A modified two-litter reproduction study in rats fed isosorbide dinitrate at 25 or 100 mg/kg/day did not reveal any affects on fertility or gestation or any remakable growth pathology in any parent or offspring fed isosorbide dinitrate as compared with rats led basal-controlled diet

Patient with glaucoma - Use with caution

Use During Pregnancy - Isosorbide dinitrate has been shown to cause a dose-related increase in embryo toxicity (increase in mummified pups) in rabbits at oral doses 35 and 150 times the maximum recommended human daily dose. There are no-adequate and well-controlled studies in pregnant women. Isordil should be used during pregnancy only if the potential benefit justfies the potential risk to the fetus

Use During Lactation - It is not known if isordil is excreted in breast milk. Because many drugs are excreted in breast milk, a decision should be made whether to discontinue nursing or to discontinue Isordil, taking into account the importance of the drug to the mother and the potential risk to the infant
Use in Children - The safety and effectiveness of Isordil in children has not been estabilished

ADVERSE EFFECTS

  1. Cutaneous vasodilation with flushing may occur
  2. Vascular headache is common and may be severe and persistent. Headache is usually relieved by the use of suitable analgesics, or by a temporary reduction in dosage, and tends to disappear after the first week or two of use
  3. Transient episodes of dizziness and weakness as well as other signs of cerebral ischemia associated with postural hypotension, may occasionally develop. Occasional individuals may exhibit marked sensitivity to the hypotensive effects of nitrates, even with the usual therapeutic dosage. Severe responses such as nausea, vomiting weakness, restlessness, pallor, perspiration, and collapse can be manifested. Alcohol may intensify this effect. Measures which fasilitate venous return (e.g. head- low or Trendelenburg position, deep breathing movement of extremities) will usually reverse the syndrome
  4. Drug rash and/or exfoliative dermatitis may occasionally occur
  5. Nausea and vomiting appear to be uncommon
  6. Marked orthostatic hypotension and rarely syncope may occur


DRUG INTERACTIONS
Nitrates may cause hypotension as a result of peripheral vasodilatation. Alcohol may enhance this effect. Patients who are prescribed isordil should be cautioned accordingly
Patient receiving antihypertensive drugs, beta adrenergic blockers, or pnenothiazines with nitrates should be observed for possible additive hypotensive effects

DOSAGE AND ADMINISTRATION
The initial dose should be no more than 5 mg since a severe hypotensive response occasionally occurs

Angina Pectoris
Sublingual Tablets (Tablet dissolve within 20 seconds) 5 mg to 10 mg sublingually every 2 to 3 hours for the prophytaxis of acute angina. Adequate controlled clinical studies demonstrating the effectiveness of chronic maintenance therapy with these dosage forms have not been reported

Oral Tablets:

  • For treatment of chronic stable angina pectoris the usual starting dose is 5 to 20 mg
  • For maintenance therapy oral dose of 10 to 40 mg every 6 hours. In order to obtain optimal therapeutic effect, it is important that the dosage of sublingual and oral forms be individualized in accordance with each patient's needs, clinical response and tolerance


Congestive Heart Failure
In selected cases of chronic congestive heart failure both sublingual and oral forms as adjunct therapy may be used. The selection of sublingual or oral isordil should be made on the basis of duration of action rather than magnitude of response, since this is major difference observed for these dosage forms
Isordil therapy should begin with the lowest effective dose and further adjusted as necessary, based on the left ventricular performance. The initial dose really depends on the assessment of how severe the heart failure is. For the treatment of acute congestive heart failure the rapidly acting sublingual form of isordil is preferred and should first administered to stabilize the patients symtoms or to determine the magnitude of hemodynamic responce, then it should be followed by the oral form for maintenance therapy.
In refractory cases isordil may be used alone or concomitantly with other vasodilators. Haemodynamic monitoring of the patient under treatment is desirable and optimal dose regimens should be determined for individual cases depending on these results
The averange recommended doses for selected cases of acute and chronic congestive heart failure are the following

Acute Congestive Heart Failure
- Sublingual tablet: 5 to 10 mg every two hours or as needed
- Oral tablet: 10 to 40 mg four times daily or as needed

Chronic Congestive Heart Failure.
- Initial dosage sublingual tablet: 5 to 10 mg every two hours or as needed
- Maintenance dosage oral tablet: 20 to 40 mg four times daily or as needed

OVERDOSAGE
Symptoms of nitrate overdosage may include the following prompt fall in blood pressure, persistent and throbbing headache, vertigo, palpitation, visual disturbances, flushed and perspiring skin (later becoming cold and cyanotic, nausea and vomiting (possibly with colic and even bloody diarrhea), syncope(especially in the upright position) methemoglobinemia with cyanosis and anoxia, initial hyperpnea, dyspnea and slow breathing, slow pulse (dicrotic and intermittent, heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions and possibly death due to circulatory collapse
It is not known what dose of the drug is associated with symptoms of overdosing or what dose of the drug would be life-threatening. The acute oral LD 50 of isosorbide dinitrate in rats was found to be approximately 1100 mg/kg of body weight. These animal experiments indicate that approximately 500 times the usual therapeutic dose would be required to produce such toxic symptoms in humans. It is not known whether the drug is dialyzable.
Suggested treatment of overdosage Prompt removal of the ingested material bay gastric lavage, if ingestion was recent and the patient is conscious. Keep the patient recumbent in a shock position and comfortably warm. Passive movement of the extremities may did venous return. Administer oxygen and artificial respiration if necessary. If methemoglobinemia is present, administer methylen blue (1% solution), 1 to 2 mg/kg intravenously.
Epinephrine is ineffective in reversing the severe hypotensive events associated with overdose it and related compounds are contraindicated in this situation.

HOW SUPPLIED
Tablet Bottle of 60 tablets @ 10 mg
Reg. No. DKL9431802610A1

Sublingual Tablet Bottle of 60 tablets @ 5 MG
Reg. No. DKL9431802574A1

STORE IN A COOL DRY PLACE (15° - 25° C).

HARUS DENGAN RESEP DOKTER

Manufactured and sold by :
PT. SUNTHI SEPURI
Tangerang, Indonesia

Under License from
Wyeth-Ayerst laboratories
Philadelphia, PA 19101 USA.
* Registered Trademark

Norvask

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Norvask
PFIZER
NORVASK®
amlodipine besylate

DESCRIPTION
Amlodipine besylate is a dihydropyridine derivative, and has the following chemical name: 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-l,4-dihydro-6-methyl-3,5pyridinedicarboxylate benzene sulphonate.
Amlodipine besylate is slightly soluble in water and sparingly soluble in ethanol and has a molecular weight of 567.1 (free base 408.9).

Amlodipine besylate is available as white, 5 mg and 10 mg emerald-shaped tablets containing 6.944 mg amlodipine besylate equivalent to 5 mg amlodipine and 13.888 mg amlodipine besylate equivalent to 10 mg amlodipine, respectively. Inert ingredients : sodium starch glycolate, mycrocrystalline cellulose, magnesium stearate, and dibasic calcium phosphate anhydrous.

ACTIONS
Pharmacodynamic Properties
Amlodipine is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.

The mechanism of the anti hypertensive 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 ischemic burden by the following two actions:
  1. 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
  2. The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).

In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset of action, acute hypotension is not a feature of amlodipine administration.

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 bath angina attack frequency and nitroglycerine tablet consumption.

In vitro studies have shown that approximately 97.5% of circulating amlodipines is bound to plasma proteins.

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.

Pharmacokinetic studies with cyclosporin have demonstrated that amlodipine does not significantly alter the pharmacokinetics of cyclosporin.

Hemodynamic studies and exercise based controlled clinical trial in NYHA Class II-IV heart failure patients have shown that amlodipine did not lead to clinical deterioration as measured by exercised 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 of mortality or combined mortality and morbidity in patients with heart failure. In the same study, in a group of patients without clinical signs or symptoms suggestive of underlying ischemic disease, a clinically and statistically significant reduction in mortality and combined mortality and morbidity was observed with amlodipine.

Pharmacokinetic properties
Absorption
After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bio availability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. Absorption of amlodipine is unaffected by consumption of food.

Bio transformation/ Elimination
The terminal plasma elimination half life is about 35-50 hours and is consistent with once daily dosing. Steady state plasma levels are reached after 7-8 days of consecutive dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.

DRUG INTERACTIONS
Interaction with Other Medicaments and Other Forms of Interaction
Amlodipine has been safely administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin - converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerine, non steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.

Studies have indicated that the co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers, and that co-administration of cimetidine did not alter the pharmacokinetics of amlodipine.

In vitro data from studies with human-plasma indicate that amlodipine has no effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin, or indomethaein).

In healthy male volunteers, the co-administration of amlodipine does not significantly alter the effect of warfarin on prothrombin response time.

Pregnancy and Lactation
Safety of amlodipine in human pregnancy or lactation has not been established. Amlodipine does not demonstrate toxicity in animal reproductive studies other than to delay parturition and prolong labor in rats at a dose level fifty times the maximum recommended dose in humans. Accordingly, use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and fetus.

Effects on Ability to Drive and Use Machines
Not applicable.

INDICATION
Therapeutic indications
Amlodiplne is indicated for treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of patients. Patients not adequately controlled on a single antihypertensive agent may benefit from the addition of amlodipine. which has been used in combination with a thiazide diuretic, beta adrenoceptor blocking agent, or an angiotensin-converting enzyme inhibitor.
Amlodipine is indicated for the first line treatment of myocardial ischemia, whether due to fixed obstruction (stable angina) and/or vasospasm/vasoconstriction (Prinzmetal's or variant angina) of coronary vasculature. Amlodipine may be used where the clinical presentation suggests a possible vasospastic/vasoconstrictive component but where vasospasm/vasoconstriction has not been confirmed. Amlodipine may be used alone, as mono therapy, or in combination with other antianginal drugs in patients with angina that is refractory to nitrates and/or adequate doses of beta blockers.

CONTRAINDICATIONS
Amlodipine is contraindicated in patients with a known sensitivity to dihydropyridines.

WARNINGS
Special Warnings and Special Precaution for Use
Use in Patients with impaired Hepatic Function
As with all calcium antagonists, amlodipine 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.

Use in Renal Failure
Amlodipine is extensively metabolized to inactive metabolites with 10% excreted as unchanged drug in the urine. Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine may be used in such patients at normal doses. Amlodipine is not dialyzable.

Use in patients with Congestive Heart Failure
In general, calcium channel blockers should be used with caution in patients with heart failure. NORVASK (5-10 mg per day) has been studied in a placebo - controlled trial of 1153 patients with NYHA Class III or IV heart failure on stable doses of ACE Inhibitor, digoxin and diuretics. Follow-up was at least 6 months, with a mean of about 14 months. There was no overall adverse effect on survival or cardiac morbidity (as defined by Life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure). NORVASK has been compared to placebo in four 8-12 week studies of patients with NY HA Class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF.

Use in the 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. Amlodiplne, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore normal dosage regimens are recommended.

ADVERSE REACTIONS
Undesirable Effects
Amlodipine is well tolerated. In placebo controlled clinical trials involving patients with hypertension or angina, the most commonly observed side effects were headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitations, and dizziness. In these clinical trials no pattern of clinically significant laboratory test abnormalities related to amlodipine has been observed.
Less commonly observed side effects in marketing experience include altered bowel habits, arthralgia, asthenia, dyspepsia, dyspnea, gingival hyperplasia, gynecomastia, impotence, increased urinary frequency, mood changes, muscle cramps, myalgia pruritus, rash, visual disturbance, and rarely arythema multiforme.

Jaundice and hepatic enzyme elevations have been reported very infrequently (mostly consistent with cholestasis). Some cases severe enough to require hospitalization have been reported in association with use of amlodipine. In many instances, causal association is uncertain.
As with other calcium channel blockers the following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation) and chest pain.

DOSAGE AND ADMINISTRATIONS
Posology and Method of Administration
For both hypertension and angina the usual initial dose is 5 mg amlodipine once daily which may be increased to a maximum dose of 10 mg depending on the individual patient's response and severity.
Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2,5 mg once daily and this dose may be used when adding amlodipine to other anti hypertensive therapy.
Majority of hypertensive patients with 5 mg/day the dose may not necessarily be increased. For those who need higher dose, Amlodipine can be increased to 7,5 mg/day with maximum dase of 10 mg/day.
The recommended dose for chronic stable or vasospastic angina is 5-10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency.
No dose adjustment of amlodipine is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.

Use in children
No experience is available on use of amlodipine in children.

OVERDOSAGE
Overdose
In humans, experience with intentional overdose is limited. Gastric lavage may be worthwhile is some cases. Available data suggest that gross over dosage could result in excessive peripheral vasodilatation with subsequent marked and probably prolonged systemic hypotension. 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 beneficial in reversing the effects of calcium channel blockage. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

SUPPLY
NORVASK® is available as 5 mg tablets, packed in boxes of 3 blisters @ 10 scored tablets. 

Reg No. DKL9219803410A1
NORVASK® is available as 10 mg tablets, packed in boxes of 3 blisters @ 10 scored tablets.
Reg. No. DKL9619803410B1.
NORVASK® for ASKES is available as 5 mg tablets, packed in boxes of 3 blisters @ 10 scored tablets. 

Reg. No. DKL9219803410Al

STORE BELOW 30°C
PRESCRIPTION ONLY



Prepared by PT. Pfizer Indonesia, PO. Box 2706 Jakarta 
Under the authority of PFIZER INC., New York, NY, U.S.A. 

Amcor

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Amcor
Amcor®
Amlodipine besylate
Calcium antagonist

Composition
Each tablet contains Amlodipine besylate 7 mg equivalent to Amlodipine 5 mg

Mechanism of Actions
Pharmacodynamic Properties
Amlodipine is a calcium ion-influx inhibitor (slow channel blocker or calcium ion antagonist) and inhibits the trans-membrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the anti-hypertensive 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 the total ischemic burden by the following two actions:
  1. Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (after load) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
  2. The mechanism of action of Amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).
In patients with hypertension, once-daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24-hour interval. Due to the slow onset of action, acute hypo-tension is not a feature of Amlodipine administration.
In patients with angina, once-daily administration of Amlodipine increase total exercise time, time to angina onset, and time to 1 mm ST segment depression and decreases bath angina attack frequency and nitroglycerin tablet consumption.
In vitro studies have shown that approximately 97.5% of circulating Amlodipine is bound to plasma proteins. Amlodipine has not been associated with any adverse metabolic effect or change in plasma lipids and is suitable for use in patients with asthma, diabetes, and gout.
Pharmacokinetic studies with cyclosporin have demonstrated that Amlodipine does not significantly alter the pharmacokinetics of cyclosporin.
Hemodynamic studies and exercise-based controlled clinical trial 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 II-IV heart failure receiving digoxin, diuretics and ACE inhibitors has shown that Amlodipine did not lead to an increase in risk of mortality or combined mortality and morbidity in patients with heart failure. In the same study, in a group of patients without clinical signs or symptoms suggestive of underlying ischemic disease, a clinically and statistically significant reductions in mortality and combined mortality and morbidity was observed with Amlodipine.

Pharmacokinetic Properties
Absorption
After oral administration of therapeutic doses, Amlodipine is well absorbed with peak blood levels between 612 hours post-dose. Absolute bio-availability has been estimated to be between 64% and 80%. The volume of distribution is approximately 21 l/kg. Absorption of Amlodipine is unaffected by consumption of food.

Bio-transformation/ Elimination
The terminal plasma elimination half life is about 35-50 hours and is consistent with once-daily dosing. Steady state plasma levels are reached after 7-8 days consecutive dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites with 10 % of the parent compound and 60% of the metabolites excreted in the urine.

Indications
Amlodipine is indicated for treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of patients. Patients not adequately control led on a single anti-hypertensive agent may benefit from the addition of Amlodipine which has been used in combination with a thiazide diuretic, beta adrenoceptor blocking agent or an angiotensin-converting enzyme inhibitors.
Amlodipine is indicated for the first-line treatment of myocardial ischemia, whether due to fixed obstruction (stable angina) and/or vasospasm/ vasoconstriction (Prinzmetal's or variant angina) of coronary vasculature. Amlodipine may be used where the clinical presentation suggests a possible vasospastic/vasoconstrictive component but where vasospasm/vasoconstriction has not been confirmed. Amlodipine may be used alone, 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.

Dosage and Administration
For both hypertension and angina the usual initial dose is 5 mg once daily which may be increased to a maximum dose of 10 mg depending on the individual patient's response and severity.
Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding Amlodipine to other anti-hypertensive therapy.
Majority of hypertensive patients with 5 mg/day the dose may not necessarily be increased. For those who need higher dose, Amlodipine can be increased to 7.5 mg/day with maximum dose of 10 mg/ day.
The recommended dose for chronic stable or vasospastic angina is 5-10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency.
No dose adjustment of Amlodipine is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.

Use in children
No experience is available on use of Amlodipine in children.

Overdosage
In humans, experiences with intentional overdose is limited. Gastric lavage may be worthwhile in some cases, Available data suggest th at gross overdosage could result in excessive peripheral vasodilatation with subsequent market and probably prolonged systemic hypotension. Clinically significant hypotensi on 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 beneficial in reversing the effect of calcium channel blockade. Since Amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

Warnings and Precautions
Use in patients with Impaired Hepatic Function
As with all calcium antagonists, Amlodipine 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.

Use in Renal Failure
Amlodipine is extensively metabolized to inactive metabolites with 10% excreted as unchanged drug in the urine. Changes in Amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine may be used in such patients at normal doses.Amlodipine is not dialyzable.

Use in patients with Congestive Heart failure
In general, calcium channel blockers should be used with caution in patients with heart failure.

Use in the 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. Amlodipine, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore, normal dosage regimens are recommended.

Pregnancy and Lactation
Safety of Amlodipine in human pregnancy or lactation have not been established. Amlodipine does not demonstrate toxicity in animal reproductive studies other than to delay parturition and prolong labor in rats at a dose level fifty times the maximum recommended dose in humans. Accordingly, use in pregnancy and lactation is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and fetus.

Effect on ability to drive and use machines
Not applicable.

Adverse Reactions
Amlodipine is well tolerated. In placebo controlled clinical trials involving patients with hypertension or angina, the most commonly observed side effect were headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing palpitations and dizziness. In these clinical trials no pattern of clinically significant laboratory test abnormalities related to Amlodipine has been observed.
Less commonly observed adverse effects in marketing experience include altered bowel habits, arthralgia, asthenia, dyspepsia, dyspnea, gingival hyperplasia, gynecomastia, impotence, increased urinary frequency, mood changes, muscle cramps, myalgia, pruritus, rash, visual disturbance, and rarely erythema multiforme.
Jaundice and hepatic enzyme elevations have been reported very infrequently (mostly consistent with cholestasis). Same cases severe enough to require hospitalization have been reported in association with use Amlodipine. In many instances, causal association is uncertain.
As with other calcium channel blockers the following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: Myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation) and chest pain.

Contraindications
Amlodipine is contraindicated in patients with a known sensitivity to dihydropyridines.

Interactions
Interaction with Other Medicament's and Other Forms of Interaction
Amlodipine has been safely administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sub-lingual nitroglycerin, non steroidal anti inflammatory drugs, antibiotics and oral hypoglycemic drugs.
Studies have indicated that the co-administration of Amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers, and that co-administration of cimetidine did not alter the pharmacokinetics of Amlodipine.
In vitro data from studies with human plasma indicate that Amlodipine has no effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin or indomethacin).
In healthy male volunteers, the co-administration of Amlodipine does not significantly alter the effect of warfarin on prothrombin response time.

Presentations
Box of   3 strips @ l0 tablets
Box of 10 strips @ 10 tablets

Storage
Store below 30°C.

Manufactured by
PT. Merck Tbk., Jakarta

Reg. No.: DKL 0715808010Al

Normoten

10:37 Add Comment
Normoten
NORMOTEN®

KOMPOSISI:
NORMOTEN® 5
Tiap tablet mengandung Amlodipine besylate setara dengan Amlodipine 5 mg

NORMOTEN® 10
Tiap tablet mengandung Amlodipine besylate setara dengan Amlodipine 10 mg

FARMAKOLOGI:
Amlodipine merupakan antagonis kalsium yang menghambat masuknya ion kalsium transmembran ke dalam jantung dan otot polos muskular.
Mekanisme antihipertensi amlodipine karena efek relaksasi langsung pada otot polos vaskular. Mekanisme amlodipine untuk angina belum sepenuhnya jelas, tetapi amlodipine dapat menurunkan beban iskemik melalui 2 cara yaitu:
  1. Amlodipine memperluas arteriola perifer dan menurunkan pertahanan perifer yang melawan kerja jantung.
  2. Mendilatasi arteri koroner dan arteriola koroner pada keadaan normal dan iskemik.
Pada pasien hipertensi dosis sekali sehari akan memberikan penurunan tekanan darah yang signifikan pada kondisi terlentang maupun pada saat berdiri pada rentang waktu 24 jam.
Karena onset amlodipine sangat lambat, hipotensi akut bukan merupakan keistimewaan amlodipine. Amlodipine tidak berhubungan dengan efek samping metabolik atau perubahan lipid dalam plasma dan sesuai untuk digunakan pada pasien asma, diabetes dan gout.
Setelah pemberian secara oral, amlodipine akan diabsorpsi dan kadar tertinggi dalam darah dicapai antara 6-12 jam setelah pemberian dosis. Bioavailabilitas diperkirakan antara 64 dan 80%. Absorpsi amlodipine tidak dipengaruhi oleh makanan.

INDIKASI:
Amlodipine digunakan untuk pengobatan hipertensi dan dapat digunakan untuk mengontrol tekanan darah pada mayoritas pasien.
Pasien yang tidak dapat dikontrol dengan penggunaan antihipertensi tunggal dapat memperoleh keuntungan dengan penambahan amlodipine yang dikombinasi dengan diuretik golongan thiazide, beta adrenoreceptor blocker, atau dengan ACE inhibitor.
Amlodipine digunakan sebagai terapi lini pertama pada iskemik miokardium Amlodipine dapat digunakan tunggal sebagai monoterapi atau kombinasi dengan obat-obat antiangina pada pasien dengan angina yang tidak dapat disembuhkan dengan nitrat dan atau beta blocker dengan dosis yang cukup. Adanya gangguan yang menetap (angina stabil) dan atau vasospasm/vasokonstriksi (Prinzmetal's atau varian angina) atau vasculatur coronary, amlodipine dapat digunakan bila
keadaan klinis menunjukan kemungkinan vasospastic/ vasokonstriktif tetapi letak vasospastic/ vasokonstriktif tidak ditegaskan.

DOSIS DAN CARA PEMBERIAN:
  1. Untuk hipertensi dan angina; dosis awal yang digunakan 5 mg amlodipine sekali sehari yang kemudian dapat ditingkatkan sampai dosis maksimum 10 mg/hari tergantung dari tingkat keparahan dan respon pasien.
  2. Pada pasien bertubuh kecil (small), pasien lemah (fragile), pasien lanjut usia atau pasien dengan insufisiensi hati bisa dimulai dengan dosis 2,5 mg per hari dan dosis ini dapat digunakan saat amlodipine digunakan bersama dengan terapi anti hipertensi.
  3. Umumnya pada pasien hipertensi dosis 5 mg/hari tidak perlu ditingkatkan jika tidak perlu. Jika pasien membutuhkan dosis tinggi, amlodipine dapat ditingkatkan menjadi 7,5 mg/hari sampai dosis maksimum 10 mg/hari.
  4. Untuk angina stabil kronis atau angina vasospastik: 5-10 mg/hari. Dosis ini diturunkan pada pasien lanjut usia dan pasien dengan insufisiensi hati.
  5. Tidak ada dosis tambahan yang dianjurkan pada Amlodipine selama penggunaan dengan diuretik thiazide, β-bloker dan penghambat enzym angiotensin.
  6. Penggunaan pada anak-anak: belum ada penelitian mengenai penggunaan amlodipine pada anak.
  7. Overdosis : pada manusia kasus-overdosis yang disengaja sangat jarang. Pada beberapa kasus, bilas lambung sangat berarti. Dari data yang ada menunjukkan bahwa overdosis secara umum dapat terjadi pada vasodilatasi perifer yang berlebih dan kemungkinan hipotensi sistemik dalam waktu lama. Hipotensi signifikan yang secara klinis disebabkan oleh penggunaan amlodipine yang overdosis memerlukan dukungan aktif sistem jantung termasuk pemantauan berkala dari fungsi jantung dan pernafasan, peningkatan kaki tangan, dan pemantauan sirkulasi volume cairan dan pengeluaran urin. Suatu vasokonstriktor dapat membantu dalam pengembalian tonus pembuluh darah dan tekanan darah, dimana tidak ada kontraindikasi dalam penggunaannya. Kalsium glukonat bermanfaat untuk membalikkan efek blok kanal kalsium. Karena amlodipine memiliki daya ikat protein yang tinggi maka dialisis sangat tidak dianjurkan.

EFEK SAMPING:
  1. Yang sering terjadi berupa sakit kepala, edema, fatique, somnolence, nyeri abdominal, palpitasi, pusing, mual dan muntah.
  2. Pada umumnya efek samping yang ditemukan di pasaran termasuk pruritus, kemerahan, dispenia, dispepsia, astenia, kejang otot, pembesaran gusi, dan sangat jarang ditemukan berbagai bentuk erithema. Sebagaimana dengan kalsium blocker lainnya, efek samping sangat jarang dilaporkan dan tidak dapat dihubungkan dengan riwayat penyakit seperti infark miokardium, aritmia (termasuk takikardi ventrikular dan febrilasi atrial), nyeri dada. Tidak ditemukan ketidaknormalan dari hasil laboratorium yang berhubungan dengan penggunaan amlodipine.

KONTRAINDIKASI:
Amlodipine dikontraindikasikan pada pasien yang sensitif dengan dihydropyridine.

PERHATIAN DAN PERINGATAN:
Amlodipine harus digunakan hati-hati pada:
  1. Pasien gagal jantung kongestif.
  2. Pada wanita hamil dan menyusui: pemberian amlodipine hanya diberikan jika tidak ada pilihan pengobatan lain yang lebih aman dan penyakit tersebut memberikan resiko yang lebih besar pada ibu dan bayi.
  3. Pasien dengan gangguan fungsi hati. Penggunaan pada pasien dengan ganguan hati kronis: dengan antagonis kalsium, waktu paruh amlodipine lebih lama pada pasien dengan gangguan menetap fungsi hati dan dosis yang dianjurkan belum dapat ditentukan. Untuk itu penggunaan obat ini harus diberikan secara hati-hati pada pasien dengan kondisi tersebut.
  4. Pasien gagal ginjal. Efek terhadap ginjal: Amlodipine secara luas dimetabolisme menjadi metabolit yang tidak aktif dimana 10% dikeluarkan dalam bentuk yang tidak berubah melalui urin. Perubahan konsentrasi amlodipine dalam plasma tidak berhubungan dengan tingkat kerusakan ginjal. Amlodipine dapat digunakan pada beberapa pasien dengan dosis normal. Amlodipine tidak dapat didialisis.
  5. Pasien lanjut usia. Penggunaan pada orang tua/lanjut usia: waktu untuk mencapai konsentrasi maksimal amlodipine dalam plasma pada pasien usia tua sama dengan pada pasien usia muda. Bersihan amlodipine cenderung berkurang dengan bertambahnya AUC dan waktu paruh eliminasi pada pasien usia tua. Amlodipine digunakan dengan dosis yang sama pada pasien tua maupun pada pasien usia muda, kedua-duanya sama-sama ditoleransi dengan baik oleh sebab itu dosis normal sangat dianjurkan.
  6. Interaksi dengan pengobatan lain dan bentuk lain dari interaksi: Amlodipine aman digunakan bersama dengan diuretik thiazide, β-bloker, penghambat enzym angiotensin, nitrat, nitrogliserin sublingual, NSAID, antibiotik dan golongan hipoglikemik oral. Penelitian menunjukan bahwa penggunaan amlodipine dengan digoksin tidak mengubah/mempengaruhi kadar serum digoksin atau bersihan ginjal digoksin dalam keadaan normal pada subyek, dan penggunaan simetidin tidak mengubah farmakokinetik amlodipine. Data in vitro dari studi pada plasma manusia menunjukkan bahwa amlodipine tidak menunjukan efek pengikatan protein dengan obat-obat yang diuji (digoksin, fenitoin, warfarin atau indometasin). Pada subjek uji pria sehat penggunaan bersama amlodipine tidak mempengaruhi efek warfarin terhadap waktu respon protrombin.
  7. Efek obat pada saat mengendarai kendaraan/ mesin : belum diketahui.

INTERAKSI OBAT:
  1. Amlodipine aman diberikan bersamaan dengan diuretik golongan thiazide, alpha blocker, beta blocker, ACE inhibitor, nitrate long acting, sublingual nitroglycerine, NSAID, antibiotik, obat hipoglikemik oral.
  2. Pemberian amlodipine tidak menghambat efek warfarin dan waktu respon protrombin.
  3. Data in vitro dari studi pada plasma manusia menyatakan bahwa amlodipine tidak memiliki efek pengikatan protein terhadap digoksin, fenitoin, warfarin atau indometasin.

KEMASAN:
NORMOTEN® 5
Dus, 3 strip @ 10 tablet
DKL 0724224210A1

NORMOTEN®10
Dus, 3 strip @ 10 tablet
DKL 0724224210B1

HARUS DENGAN RESEP DOKTER

SIMPAN Dl BAWAH SUHU 30°C
TERLINDUNG DARI CAHAYA

PT SOHO INDUSTRI PHARMASI
JAKARTA- INDONESIA

Intervask

11:32 Add Comment
Intervask
INTERVASK®
TABLET

KOMPOSISI:
INTERVASK® 5 Tablet
Tiap tablet mengandung:
Amlodipine besylate setara dengan
Amlodipine .................... 5 mg

INTERVASK® 10 Tablet
Tiap tablet mengandung:
Amlodipine besylate setara dengan
Amlodipine .................... 10 mg

CARA KERJA:
Amlodipine adalah inhibitor influks kalsium (slow channel blocker atau antagonis ion kalsium) dan menghambat influks ion-ion kalsium transmembran ke dalam jantung dan otot polos.

INDIKASI:
Amlodipine diindikasikan untuk pengobatan hipertensi dan dapat digunakan sebagai bahan tunggal untuk mengontrol tekanan darah pada sebagian besar penderita. Penderita-penderita yang tidak cukup terkontrol bila hanya menggunakan obat antihipertensi tunggal dapat lebih menguntungkan dengan pemberian Amlodipine yang dikombinasikan dengan diuretik thiazide, inhibitor β-adrenoreceptor, atau inhibitor angiotensin-converting enzyme.
Amlodipine juga digunakan untuk pengobatan Prinzmetal variant angina dan chronic stable angina pectotis. Amlodipine dapat digunakan sendiri sebagai monoterapi atau dikombinasikan dengan obat-obat antiangina lainnya.

KONTRAINDIKASI :
Pasien yang sensitif terhadap Dihydropyridine. Syok kardiogenik, aortic stenosis yang nyata secara klinik, angina tidak stabil (kecuali Prinzmetal angina).

EFEK SAMPING:
Amlodipine ditoleransi dengan baik. Pada penelitian klinik dengan kontrol plasebo yang mencakup penderita dengan hipertensi dan angina, efek samping yang umum terjadi adalah sakit kepala, edema, lelah, mengantuk, mual, sakit perut, flushing, jantung berdebar, dan pusing.
Tidak ada kelainan-kelainan tes laboratorium yang signifikan secara klinis yang berkaitan dengan Amlodipine.


PERINGATAN / PERHATIAN:
  • Penggunaan pada Penderita dengan Kegagalan Fungsi Hati: Seperti semua kalsium antagonis, waktu paruh Amlodipine lebih panjang pada penderita dengan kegagalan fungsi hati dan rekomendasi dosis belum ditetapkan. Sebaiknya perlu perhatian khusus penggunaan obat ini pada penderita dengan kegagalan fungsi hati.
  • Penggunaan pada Penderita dengan Kegagalan Ginjal: Amlodipine sebagian besar dimetabolisme menjadi metabolit inaktif dimana 10% diekskresikan dalam bentuk utuh melalui urin. Perubahan-perubahan kadar Amlodipine dalam plasma tidak ada korelasi dengan derajat kegagalan ginjal. Amlodipine dapat digunakan pada penderita tersebut dengan dosis normal. Arnlodipine tidak dapat didialisis
  • Penggunaan pada Penderita Kegagalan Jantung Kongestif : Secara umum, calcium channel blocker harus digunakan dengan hati-hati pada penderita kegagalan jantung.
  • Kehamilan dan Menyusui: Keamanan penggunaan Amlodipine pada ibu hamil dan menyusui belum dibuktikan. Untuk itu, penggunaan pada ibu hamil dan menyusui hanya direkomendasikan bila tidak ada alternatif lain yang lebih aman dan bila penyakitnya itu sendiri membawa resiko yang lebih besar terhadap ibu dan anak.
  • Penggunaan pada Penderita Lanjut Usia: Ada beberapa fakta bahwa usia mempengaruhi profil farmakokinetik Amlodipine yaitu meningkatnya konsentrasi dalam plasma dan waktu paruh yang lebih panjang pada subyek lanjut usia. Meskipun demikian, tidak ada peringatan khusus untuk kelompok ini.

INTERAKSI OBAT:
Amlodipine aman diberikan bersama-sama dengan diuretik thiazide, α-blocker, β-blocker, inhibitor angiotensin-converting enzyme, long-acting nitrat, nitroglycerine sublingual, obat-obat antiinflamasi non steroid, antibiotika, dan obat hipoglikemik oral.
Pada penelitian khusus menyebutkan bahwa pemberian Amlodipine bersama-sama Digoxin tidak mengubah kadar Digoxin dalam serum dan klirens renal Digoxin pada sukarelawan normal, dan pemberian bersama-sama dengan Cimetidine tidak mengubah farmakokinetika Amlodipine.
Data in-vitro dari penelitian dengan plasma manusia menyebutkan bahwa Amlodipine tidak mempunyai efek pada ikatan protein dari obat-obat yang diuji (Digoxin, Phenytoin, Warfarin atau Indomethacin).

ATURAN PAKAI:
Untuk hipertensi maupun angina, dosis awal adalah 5 mg Amlodipine satu kali sehari, dapat ditingkatkan sampai dosis maksimum 10 mg tergantung respon pasien secara individual dan berat penyakit.
Pasien bertubuh kecil, pasien yang lemah atau pasien lanjut usia, atau pasien dengan gagal fungsi hati dapat dimulai dengan dosis 2,5 mg Amlodipine satu kali sehari dan dosis ini dapat digunakan ketika Amlodipine ditambahkan dengan terapi antihipertensi lain.
Dosis yang dianjurkan untuk chronic stable atau angina vasospastik adalah 5-10 mg, dan dosis yang lebih rendah untuk pasien lanjut usia dan pasien gagal fungsi hati.
Tidak diperlukan penyesuaian dosis Amlodipine pada pemberian bersama-sama dengan diuretik thiazide, β-blocker dan inhibitor angiotensin-converting enzyme.
Untuk anak-anak: Tidak ada penelitian penggunaan Amlodipine pada anak-anak.

OVERDOSIS:
Pada manusia, penelitian mengenai overdosis masih terbatas. Dari data yang ada menunjukkan bahwa overdosis dapat menyebabkan vasodilatasi perifer yang berlebihan dengan tanda selanjutnya berupa hipotensi sistemik yang lebih lama. Hipotensi yang signifikan secara klinik karena overdosis Amlodipine memerlukan dukungan kardiovaskular aktif termasuk pemantauan jantung dan fungsi pernapasan, peninggian anggota badan, dan perhatian terhadap volume cairan sirkulasi dan pengeluaran urin. Bahan vasokonstriktor dapat membantu memulihkan tegangan vaskular dan tekanan darah, diberikan bila tidak ada kontraindikasi terhadap penggunaannya. Calcium gluconate intravena dapat bermanfaat dalam membalikkan efek penghambatan kalsium channel, Karena Amlodipine sebagian besar terikat protein, dialisis tidak menguntungkan.

KEMASAN:
INTERVASK® 5 Tablet
Kotak berisi 3 strip @ 10 tablet
Reg. No.: DKL0717622110A1

INTERVASK® 10 Tablet
Kotak bensi 3 strip @ 10 tablet
Reg. No.: DKL0717622110B1

HARUS DENGAN RESEP DOKTER

SIMPAN DI BAWAH 30°C
TERLINDUNG DARI CAHAYA

Diproduksi oleh:
PT. Interbat
Jl. H.R.M. Mangundiprojo no. 1
Buduran, Sidoarjo-61252
Jawa Timur, Indonesia

Tensivask

14:25 Add Comment
Tensivask
TENSIVASK®
Tablet

Komposisi:
TENSIVASK® 5 mg
Tiap tablet mengandung:
Amlodipine .................................... 5 mg

TENSIVASK® 10 mg
Tiap tablet mengandung:
Amlodipine .................................... 10 mg

Farmakologi:
Amlodipine adalah inhibitor influks kalsium (slow channel blocker atau antagonis ion kalsium) dan menghambat influks ion-ion kalsium transmembran ke dalam jantung dan otot polos.
Mekanisme kerja antihipertensi amlodipine karena efek relaksasi secara langsung pada otot polos vaskular, Mekanisme yang tepat dari amlodipine untuk menghilangkan angina belum sepenuhnya diketahui, tetapi amiodipin memperkecil iskemia total dengan dua cara kerja berikut:
  • Amlodipine menimbulkan dilatasi arteriola perifer sehingga memperkecil tahanan perifer total (afterload) terhadap kerja jantung. Karena tidak menimbulkan refleks takikardia, maka tidak ada muatan terhadap jantung sehingga menurunkan konsumsi energi miokardial dan kebutuhan oksigen, hal ini dapat meningkatkan efektivitas amlodipine terhadap iskemia miokardial.
  • Amlodipine menimbulkan dilatasi arteri koroner utama dan arteriola koroner, baik pada keadaan normal maupun iskemia. Dilatasi ini meningkatkan penyampaian oksigen miokardial pada penderita dengan spasme arteri koroner (Prinzmetal's atau angina varian).

Farmakokinetika:
Setelah pemberian dosis terapeutik secara oral, amlodipine diabsorpsi dengan baik dan kadar puncak dalam plasma tercapai 6-12 jam setelah pemberian. Volume distribusi amlodipine kira-kira 20 liter/kg. Waktu paruh eliminasi plasma terminal adalah sekitar 35-50 jam dan konsisten pada pemberian dosis sehari sekali. Kadar mantap dalam plasma tercapai 7-8 hari setelah pemberian secara terus menerus sehari sekali. Sebanyak 97,5% amlodipine dalam sirkulasi terikat protein plasma.
Amlodipine sebagian besar dimetabolisme menjadi metabolit inaktif dimana 10% senyawa asal dan 60% metabolit diekskresikan melalui urin. Pada penderita hipertensi, pemberian dosis sehari sekali memberikan penurunan tekanan darah yang signifikan secara klinis baik pada posisi tertentang maupun berdiri setelah interval waktu 24 jam. Karena mula kerja yang lambat maka tidak terjadi hipotensi akut setelah pemberian amlodipine.
Pada penderita angina, pemberian dosis sehari sekali meningkatkan waktu exercise total dan menurunkan frekuensi serangan angina dan konsumsi tablet nitrogliserin. Amlodipine tidak mempengaruhi efek metabolit atau perubahan-perubahan lipid (lemak) dalam plasma.

Indikasi:
amlodipine diindikasikan untuk pengobatan hipertensi dan dapat digunakan sebagai bahan tunggal untuk mengontrol tekanan darah pada sebagian besar penderita. Penderita-penderita yang tidak cukup terkontrol bila hanya menggunakan obat antihipertensi tunggal dapat lebih menguntungkan dengan pemberian amlodipine yang dikombinasi dengan diuretik thiazida, inhibitor β-adreroreceotor atau inhibitor angiotensin-converting enzym.
Amlodipine diindikasikan untuk pengobatan iskemia myokardial apakah karena obstruksi fixed (angina stabil) dan atau vasospasme/ vasokonstriksi (Prinzmetal's atau angina varian) dari pembuluh darah koroner. Amlodipine dapat digunakan dimana gambaran klinik menunjukkan suatu kemungkinan komponen vasospastik/ vasokonstriktif tetapi belum nampak adanya vasospasme/ vasokonstriksi. Amlodipine dapat digunakan sendiri sebagai monoterapi atau dikombinasikan dengan obat-obat antiangina lainnya terutama pada penderita angina yang sukar disembuhkan dengan nitrat dan atau dengan β-blocker pada dosis yang memadai.

Kontraindikasi:
Amlodipine dikontraindikasikan pada penderita yang sensitif terhadap dihidropiridin.

Dosis:
  • Untuk hipertensi: Dosis lazim adalah 5 mg amlodipine satu kali sehari, dapat ditingkatkan sampai dosis maksimum 10 mg tergantung respons pasien secara individual dan berat penyakit. Bayi, pasien yang lemah (fragile), pasien lanjut usia atau pasien dengan gagal fungsi hati dapat dimulai dengan dosis 2,5 mg amlodipine satu kali sehari dan dosis ini dapat digunakan ketika amlodipine ditambahkan dengan terapi antihipertensi lain. Sebagian besar pasien hipertensi dengan dosis pemakaian 5 mg setiap hari tidak pertu peningkatan dosis. Bagi mereka yang memerlukan dosis lebih tinggi, amlodipine dapat ditingkatkan menjadi 7,5 mg setiap hari dengan dosis maksimum 10 mg setiap hari. Dosis yang dianjurkan untuk chronic stable atau angina vasospastik adalah 5 - 10 mg, dan dosis yang lebih rendah untuk pasien lanjut usia dan pasien gagal fungsi hati.
  • Untuk anak-anak : Sampai saat ini penggunaan amlodipine untuk anak-anak tidak pernah dilaporkan.

Overdosis:
Walaupun tidak ada penelitian yang menyebutkan tentang overdosis amlodipine, tetapi dari data yang ada menunjukkan bahwa overdosis dapat menyebabkan vasodilatasi perifer yang berlebihan dengan tanda selanjutnya berupa hipotensi sistemik yang lebih lama.
Hipotensi yang signifikan secara klinik karena overdosis amlodipine memerlukan dukungan kardiovaskular aktif termasuk pemantauan jantung dan fungsi pernapasan, peninggian anggota badan, dan perhatian terhadap volume cairan sirkulasi dan pengeluaran urin. Bahan vasokonstriktor dapat membantu memulihkan tegangan vaskular dan tekanan darah, diberikan bila tidak ada kontraindikasi terhadap penggunaannya. Karena amlodipine sebagian besar terikat protein, dialisis tidak menguntungkan.
Pada beberapa kasus, pencucian lambung dapat membantu menurunkan laju absorpsi amlodipine.

Efek samping:
Amlodipine ditoleransi dengan baik. Pada penelitian klinik dengan kontrol plasebo yang mencakup penderita dengan hipertensi dan angina, efek samping yang umum terjadi adalah sakit kepala, edema, lelah, mual, flushing, dan pusing-pusing. Tidak ada kelainan-kelainan tes laboratorium yang signifikan secara klinis yang berkaitan dengan amlodipine.

Peringatan dan perhatian:
  • Penggunaan pada penderita dengan kegagalan ginjal.
    • Amlodipine sebagian besar dimetabolisme menjadi metabolit inaktif dimana 10% diekskresikan dalam bentuk utuh melalui urin. Perubahan-perubahan kadar amlodipine dalam plasma tidak ada korelasi dengan derajat kegagalan ginjal. Amlodipine dapat digunakan pada penderita tersebut dengan dosis normal.
    • Amlodipine tidak dapat didialisis.
  • Penggunaan pada penderita dengan kegagalan fungsi hepar.
    • Waktu paruh amlodipine lebih panjang pada penderita dengan kegagalan fungsi hepar dan rekomendasi dosis belum ditetapkan. Sebaiknya perlu perhatian khusus penggunaan obat ini pada penderita dengan kegagalan fungsi hepar.
  • Penggunaan pada ibu hamil dan menyusui.
    • Keamanan penggunaan amlodipine pada ibu hamil dan menyusui belum dibuktikan. Amlodipine tidak menunjukkan toksisitas pada penelitian reproduktif pada binatang selain memperpanjang parturisi dan kerja pada tikus percobaan yang diberi dosis 50 kali dosis maksimum yang direkomendasikan pada manusia. Berdasarkan itu, penggunaan pada ibu hamil dan menyusui hanya direkomendasikan bila tidak ada alternatif lain yang lebih aman dan bila penyakitnya itu sendiri membawa resiko yang lebih besar terhadap ibu dan anak.
  • Penggunaan pada anak-anak
    • Karena tidak ada percobaan klinik pada penderita pediatrik, amlodipine tidak direkomendasikan secara langsung.
  • Penggunaan pada penderita lanjut usia.
    • Walaupun penderita lanjut usia kemungkinan memiliki kadar amlodipine dalam plasma yang lebih tinggi dibanding penderita yang lebih muda, tetapi waktu paruh eliminasi terminalnya sama. Amlodipine yang digunakan pada dosis yang sama baik pada penderita lanjut usia maupun penderita yang lebih muda, sama-sama ditoleransi. Sehingga untuk penderita lanjut usia direkomendasikan pemberian dosis normal.

Interaksi obat:
Amlodipine aman diberikan bersama-sama dengan diuretik thiazida, β-blocker, inhibitor angiotensin-converting enzym, long-acting nitrat, nitrogliserin sublingual, obat-obat antiinflamasi non steroid, antibiotika, dan obat hipoglikemik oral. Pada penelitian khusus menyebutkan bahwa pemberian amlodipine bersama-sama digoksin tidak mengubah kadar digoksin dalam serum dan klirens renal digoksin pada sukarelawan normal, dan pemberian bersama-sama dengan simetidin tidak mengubah farmakokinetika amlodipine. Data in-vitro dari penelitian dengan plasma manusia menyebutkan bahwa amlodipine tidak mempunyai efek pada ikatan protein dari obat-obat yang diuji (digoksin, fenitoin, warfarin atau indometasin).

Kemasan dan Nomor Registrasi:
TENSIVASK® 5 mg:
Kotak berisi 5 blister @ 10 tablet, DKL9405014110Al
Botol @ 30 tablet, DKL9405014110Al

TENSIVASK® 10 mg:
Kotak berisi 5 blister @ 10 tablet, DKL0205014110B1

HARUS DENGAN RESEP DOKTER.

SIMPAN PADA SUHU DI BAWAH 30°C. TERLINDUNG DARI CAHAYA.

Diproduksi oleh
PT Dexa Medica
JI. Letjen. Bambang Utoyo 138
Palembang-Indonesia

Bahan berkhasiat dari Pfizer

Molesco

14:10 Add Comment
Molesco
Molesco®
Amlodipine
Kaplet

KOMPOSISI:
Molesco® 5 mg
Tiap kaplet mengandung:
Amlodipine besylate 6,944 mg setara dengan Amlodipine 5 mg.

Molesco® 10 mg
Tiap kaplet mengandung:
Amlodipine besylate 13,888 mg setara dengan Amlodipine 10 mg.

FARMAKOLOGI:
Amlodipine adalah inhibitor influks kalsium (slow channel blocker atau antagonis ion kalsium) dan menghambat influks ion-ion kalsium transmembran ke dalam jantung dan otot polos.
Mekanisme kerja antihipertensi Amlodipine karena efek relaksasi secara langsung pada otot polos vaskular. Mekanisme yang tepat dari Amlodipine untuk menghilangkan angina belum sepenuhnya diketahui, tetapi Amlodipine memperkecil iskemia total dengan dua cara kerja berikut:
  1. Amlodipine menimbulkan dilatasi arteriola perifer sehingga memperkecil tahanan perifer total (afterload) terhadap kerja jantung. Karena tidak menimbulkan refleks takikardia, maka tidak ada muatan terhadap jantung sehingga menurunkan konsumsi energi miokardial dan kebutuhan oksigen, hal ini dapat meningkatkan efektivitas Amlodipine terhadap iskemia miokardial.
  2. Amlodipine menimbulkan dilatasi arteri koroner utama dan arteriola koroner, baik pada keadaan normal maupun iskemia. Dilatasi ini meningkatkan penyampaian oksigen miokardial pada penderita dengan spasme arteri koroner (Prinzmetal's atau angina varian).

FARMAKOKINETIKA:
Setelah pemberian dosis terapeutik secara oral, Amlodipine diabsorpsi dengan baik dan kadar puncak dalam plasma tercapai 6 - 12 jam setelah pemberian. Volume distribusi Amlodipine kira-kira 20 liter/kg. Waktu paruh eliminasi plasma terminal adalah sekitar 35 - 50 jam dan konsisten pada pemberian dosis sehari sekali. Kadar mantap dalam plasma tercapai 7 - 8 hari setelah pemberian secara terus menerus sehari sekali. Sebanyak 97,5% Amlodipine dalam sirkulasi terikat protein plasma.
Amlodipine sebagian besar dimetabolisme menjadi metabolit inaktif dimana 10% senyawa asal dan 60% metabolit diekskresikan melalui urine. Pada penderita hipertensi, pemberian dosis sehari sekali memberikan penurunan tekanan darah yang signifikan baik pada posisi terlentang maupun berdiri setelah interval waktu 24 jam. Karena mula kerja yang lambat maka tidak terjadi hipotensi akut setelah pemberian Amlodipine.
Pada penderita angina, pemberian dosis sehari sekali meningkatkan waktu exercise total dan menurunkan frekuensi serangan angina dan konsumsi tablet nitrogliserin. Amlodipine tidak mempengaruhi efek metabolit atau perubahan-perubahan lipid (lemak) dalam plasma.

INDIKASI:
Amlodipine diindikasikan untuk pengobatan hipertensi dan dapat digunakan sebagai bahan tunggal untuk mengontrol tekanan darah pada sebagian besar penderita. Penderita-penderita yang tidak cukup terkontrol bila hanya menggunakan obat antihipertensi tunggal dapat lebih menguntungkan dengan pemberian Amlodipine yang dikombinasi dengan diuretik thiazida, inhibitor β-adrenoreceptor, atau inhibitor angiotensin-converting enzym.
Amlodipine diindikasikan untuk pengobatan iskemia myokardial apakah karena obstruksi fixed (angina stabil) dan atau vasospasme/vasokonstriksi (Prinzmetal's atau angina varian) dari pembuluh darah koroner. Amlodipine dapat digunakan dimana gambaran klinik menunjukkan suatu kemungkinan komponen vasospastik/vasokonstriktif tetapi belum nampak adanya vasospasme/vasokonstriksi. Amlodipine dapat digunakan sendiri sebagai monoterapi atau dikombinasikan dengan obat-obat antiangina lainnya terutama pada penderita angina yang sukar disembuhkan dengan nitrat dan atau dengan β-blocker pada dosis yang memadai.

KONTRAINDIKASI :
Amlodipine dikontraindikasikan pada penderita yang sensitif terhadap dihidropiridin.

DOSIS:
  1. Untuk hipertensi: Dosis lazim adalah 5 mg Amlodipine satu kali sehari, dapat ditingkatkan sampai dosis maksimum 10 mg tergantung respons pasien secara individual dan berat penyakit. Pasien yang lemah (fragile), pasien lanjut usia atau pasien dengan gagal fungsi hati dapat dimulai dengan dosis 2,5 mg Amlodipine satu kali sehari dan dosis ini dapat digunakan ketika Amlodipine ditambahkan dengan terapi antihipertensi lain. Sebagian besar pasien hipertensi dengan dosis pemakaian 5 mg setiap hari tidak perlu peningkatan dosis. Bagi mereka yang memerlukan dosis lebih tinggi, Amlodipine dapat ditingkatkan menjadi 7,5 mg setiap hari dengan dosis maksimum 10 mg setiap hari. Dosis yang dianjurkan untuk chronic stable atau angina vasospastik adalah 5 - 10 mg, dan dosis yang lebih rendah untuk pasien lanjut usia dan pasien gagal fungsi hati.
  2. Untuk anak-anak: Sampai saat ini penggunaan Amlodipine untuk anak-anak tidak pernah dilaporkan.

OVERDOSIS:
Walaupun tidak ada penelitian yang menyebutkan tentang overdosis Amlodipine, tetapi dari data yang ada menunjukkan bahwa overdosis dapat menyebabkan vasodilatasi perifer yang berlebihan dengan tanda selanjutnya berupa hipotensi sistemik yang lebih lama.
Hipotensi yang signifikan secara klinik karena overdosis Amlodipine memerlukan dukungan kardiovaskular aktif termasuk pemantauan jantung dan fungsi pernapasan, peninggian anggota badan, dan perhatian terhadap volume cairan sirkulasi dan pengeluaran urine. Bahan vasokonstriktor dapat membantu memulihkan tegangan vaskular dan tekanan darah, diberikan bila tidak ada kontraindikasi terhadap penggunaannya. Karena Amlodipine sebagian besar terikat protein, dialisis tidak menguntungkan.
Pada beberapa kasus, pencucian lambung dapat membantu menurunkan laju absorpsi Amlodipine.

EFEK SAMPING:
Amlodipine dapat ditoleransi dengan baik. Efek samping yang umumnya terjadi adalah sakit kepala, edema, rasa lelah, rasa kantuk, mual, sakit perut, rasa panas, berdebar-debar dan pusing. Efek samping yang jarang terjadi mencakup gatal-gatal, ruam, sesak napas, nyeri pada ulu hati, rasa lemas, kejang otot, rasa sakit pada gusi dan sangat jarang sekali kemerahan pada kulit. Sama seperti Calcium antagonis lainnya, kejadian seperti ini jarang dilaporkan dan tidak dapat dibedakan dari kejadian alami yang mendasari penyakit gagal jantung (termasuk ventricular tachycardia dan atrial fibrillation ) dan sakit pada dada.

PERINGATAN DAN PERHATIAN:
  1. Penggunaan pada penderita dengan kegagalan ginjal.
    • Amlodipine sebagian besar dimetabolisme menjadi metabolit inaktif dimana 10% diekskresikan dalam bentuk utuh melalui urine. Perubahan-perubahan kadar Amlodipine dalam plasma tidak ada korelasi dengan derajat kegagalan ginjal. Amlodipine dapat digunakan pada penderita tersebut dengan dosis normal. Amlodipine tidak dapat didialisis.
  2. Penggunaan pada penderita dengan kegagalan fungsi hepar.
    • Waktu paruh Amlodipine lebih panjang pada penderita dengan kegagalan fungsi hepar dan rekomendasi dosis belum ditetapkan. Sebaiknya perlu perhatian khusus penggunaan obat ini pada penderita dengan kegagalan fungsi hepar
  3. Penggunaan pada ibu hamil dan menyusui.
    • Keamanan penggunaan Amlodipine pada ibu hamil dan menyusui belum dibuktikan. Amlodipine tidak menunjukkan toksisitas pada penelitian reproduktif pada binatang selain memperpanjang parturisi dan kerja pada tikus percobaan yang diberi dosis 50 kali dosis maksimum yang direkomendasikan pada manusia. Berdasarkan itu, penggunaan pada ibu hamil dan menyusui hanya direkomendasikan bila tidak ada alternatif lain yang lebih aman dan bila penyakitnya itu sendiri membawa risiko yang lebih besar terhadap ibu dan anak.
  4. Penggunaan pada penderita lanjut usia.
    • Walaupun penderita lanjut usia kemungkinan memiliki kadar Amlodipine dalam plasma yang lebih tinggi dibanding penderita yang lebih muda, tetapi waktu paruh eliminasi terminalnya sama. Amlodipine yang digunakan pada dosis yang sama baik pada penderita lanjut usia maupun penderita yang lebih muda, sama-sama ditoleransi. Sehingga untuk penderita lanjut usia direkomendasikan pemberian dosis normal.

INTERAKSI OBAT:
Amlodipine aman diberikan bersama-sama dengan diuretik thiazida, β-blocker, inhibitor angiotensin-converting enzym, long-acting nitrat, nitrogliserin sublingual, obat-obat antiinflamasi non steroid, antibiotika, dan obat hipoglikemik oral. Pada penelitian khusus pemberian Amlodipine bersama-sama digoksin tidak mengubah kadar digoksin dalam serum dan klirens renal digoksin pada sukarelawan normal, dan pemberian bersama-sama dengan simetidin tidak mengubah farmakokinetika Amlodipine. Amlodipine tidak mempunyai efek pada ikatan protein dari obat-obat yang diuji (digoksin, fenitoin, warfarin atau indometasin).

KEMASAN:
Dus, 5 strip @ 10 kaplet 5 mg
No. Reg.DKL0802501404A1

Dus, 5 strip @ 10 kaplet 10 mg
No. Reg. DKL0802501404B1

Simpan pada suhu kamar (25 - 30)° C, terlindung dari cahaya.

HARUS DENGAN RESEP DOKTER

Diproduksi oleh:
PT. PHARMASI BINANGKIT
Majalengka - Indonesia

Farsorbid

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Farsorbid
Farsorbid®
Isosorbide Dinitrate

COMPOSITION
Farsorbid® 5
Each sublingual tablet contains :
Isosorbide Dinitrate 5 mg

Farsorbid® 10
Each tablet contains :
Isosorbide Dinitrate 10 mg

Farsorbid® Injection
Each mL injection contains :
Isosorbide Dinitrate 1 mg in sterile isotonic saline

PHARMACOLOGY
Isosorbide Dinitrate is a direct acting vasodilator. It reduce myocardial oxygen requirements through its effects on the systemic circulation. Its major systemic action is a reduction in venous tone, which leads to pooling of blood in peripheral veins decreased venous return, and reduced ventricular volume and myocardial tension (preload). It dilates the large epicardial (conductance) arteries but has little effect on intramyocardial (resistance) vessels. In the normal non-ischemic myocardium, coronary blood flow may increase temporarily and then decrease because of the fall in central aortic pressure.
Isosorbide Dinitrate is believed to improve angina of effort through its effects on the peripheral circulation however, its haemodynamic action are not always closely correlated with antianginal activity, and increase in regional myocardial blood flow may contribute to the therapeutic response. It relieves variant angina primarily through effect on the coronary circulation.

INDICATIONS
Farsorbid® sublingual tablet
Is indicated for the treatment and prophylaxis of angina pectoris.
Farsorbid® injection
Is indicated in the treatment of unresponsive left ventricular failure secondary to acute myocardial infarction, unresponsive left ventricular failure of various aetiology and severe or unstable angina pectoris.

DOSAGE AND ADMINISTRATION
Farsorbid® 5
Usual Adult dose :
1 to 2 sublingual tablet every two to three hours as needed.
Usual pediatric dose : dosage has not been established.

Farsorbid® 10
Usual Adult dose :
Oral, 10 mg four times a day, the dosage being adjusted as needed and-tolerated.
Before sleeping, 10 mg use for the prophylaxis of angina pectoris.

Farsorbid® Injection
Dosage:
The dose employed must be adjusted according to the patient's response. In general a dose of between 2 and 7 mg per hour is suitable although doses as high as 10 mg per hour may be necessary.
Children:
The safety and efficacy of Farsorbid® injection has not been yet established in children.

Administration:
Farsorbid® injection is supplied as a concentrated solution and should never be injected directly. It should always be administered as an intravenous admixture with a suitable vehicle such as Sodium Chloride Injection B.P. or Dextrose Injection B.P. Prepared Farsorbid® injection admixtures are always given by intravenous infusion or with the aid of a syringe pump. During administration, there should be close monitoring of the patient's blood pressure and pulse. Admixtures are prepared by exchanging the required volume of Farsorbid® injection with an equal volume of the infusion vehicle.

WARNINGS AND PRECAUTIONS
Farsorbid® sublingual tablet
  • Should be given with caution in patient at pregnancy or nursing mother, because problems in humans have not been documented however, risk benefit must be considered. Isosorbide Dinitrate may develop tolerance and cross tolerance to other nitrates and nitrites.
  • Use of this medication should be carefully considered when the following medical problem exist anemia, hyperthyroidism, intracranial pressure (increased), myocardial infarction (recent).
Farsorbid® injection
Close attention to pulse and blood pressure is necessary during the administration of Farsorbid® injection.
Farsorbid® injection should be used with caution in patients who are predisposed to closed angle glaucoma.
This product should not be used during pregnancy or lactation unless considered essential by the physicians.
Farsorbid® injection should be used with caution in patients suffering from hypothyroidism, malnutrition, sever liver or renal disease or hypothermia.

SIDE EFFECTS
  • Incidence more frequent: orthostatic hypotension, flushing of face and neck, headache, nausea or vomiting, rapid pulse.
  • Incidence rare: skin rash.
  • Whilst sharp falls in systemic arterial pressure can give rise to symptoms of cerebral flow deficiency and decreased coronary perfusion, clinical experience with Farsorbid® injection has shown that this is not normally a problem. This is consistent with the known vasodilatory effects of Isosorbide Dinitrate which occur predominantly on the venous rather than on the arterial side of the circulation. In common with other nitrates, headaches and nausea may occur during administration.

CONTRAINDICATIONS
  • Farsorbid® sublingual tablet, is contraindicated in patients who have hypersensitivity reactions to nitrates, and glaucoma.
  • Farsorbid® injection, should not be used in the treatment of cardiogenic shock unless some means of maintaining an adequate diastolic pressure is undertaken, for example, by concurrent administration of an inotrope. Farsorbid® injection is contraindicated in circulatory collapse and severe hypotension. Farsorbid® injection, should not be given to patients with known sensitivity to nitrates. Farsorbid® injection should not be used in patients with marked anemia, head trauma, cerebral haemorrhage, severe hypotension or hypovolaemia.

DRUG INTERACTIONS
  • Alcohol (moderate or excessive amounts) or antihypertensives or vasodilators (other) concurrent use may intensify the orthostatic hypotensive effects of Isosorbide Dinitrate. 
  • Sympathomimetics (such as phenylephrine, ephedrine, or epinephrine) concurrent use may reduce the antianginal effect of Isosorbide Dinitrate.

STORAGE
Store between 25° - 30°C. Protect from light

PRESENTATION
Farsorbid® 5
Box, 10 strips @ 10 sublingual tablets, Reg. No. DKL8831500474A1

Farsorbid® 10
Box, 10 strips @ 10 tablets, Reg. No. DKL9031527710A1

Farsorbid® injection
Box, 2 vials @ 10 mL, Reg. No. DKL0631526443A1

ON MEDICAL PRESCRIPTION ONLY

Manufactured by :
PT. PRATAPA NIRMALA
Tangerang - Indonesia

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