Extor COMPOSITION
Every single tablet with a film coating includes:Amlodipine+Valsartan.
✓ 5mg 80mg
✓ 5mg 160mg
✓ 10mg 160mg
WARNING: AVOID USE IN PREGNANCY
When you are pregnant, you should discontinue the use of Amlodipine and Valsartan as soon as possible. These drugs can act directly on the renin-angiotensin system, which could harm your developing baby.THERAPEUTIC INDICATIONS
Treatment of Essential
Hypertension:
Amlodipine Valsartan is prescribed for adults whose blood pressure remains inadequately controlled with either amlodipine or valsartan monotherapy.
POSOLOGY AND METHOD OF ADMINISTRATION:
PosologyOne tablet of amlodipine and valsartan per day is the suggested dosage.
Patients whose blood pressure cannot be sufficiently controlled with amlodipine 5 mg or valsartan 80 mg alone may be prescribed amlodipine + valsartan 5 mg+80 mg.
Patients whose blood pressure cannot be sufficiently controlled with amlodipine 5 mg or valsartan 160 mg alone may be prescribed amlodipine + valsartan 5 mg + 160 mg.
Patients whose blood pressure is not sufficiently managed by amlodipine 10 mg, valsartan 160 mg, or amlodipine + valsartan 5 mg + 160 mg may be given Amlodipine Valsartan 10 mg + 160 mg.
Amlodipine + Valsartan can be used with or without food.
Titrating the dose of each component (e.g., valsartan and amlodipine) is recommended prior to transitioning to a fixed-dose combination. Direct conversion from monotherapy to a fixed-dose combination may be taken into consideration when clinically suitable.
Patients using individual pills or capsules containing amlodipine and valsartan may be switched to Amlodipine + Valsartan, which contains the same component doses, for convenience's sake.
Elderly (age 65 years or over)
When raising the dosage in senior patients, care should be taken. The lowest dose of either amlodipine monotherapy or the amlodipine component should be utilised for transitioning suitable elderly hypertensive patients to amlodipine or amlodipine + valsartan.Paediatric population:
It has not been determined whether amlodipine plus valsartan is safe or effective for children under the age of 18. There are no available data.Method of administration:
Oral useIt is recommended to take Amlodipine + Valsartan with some water.
CONTRAINDICATIONS:
•Severe hepatic impairment, biliary cirrhosis or cholestasis.
• Concomitant use of Amlodipine + Valsartan with aliskiren-containing products in patients excipients. with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²).
• Second and third trimesters of pregnancy.
• Severe hypotension.
• Shock (including cardiogenic shock).
• Obstruction of the outflow tract of the left ventricle (e.g. hypertrophic obstructive cardiomyopathy and high-grade aortic stenosis).
• Haemodynamically unstable heart failure after acute myocardial infarction.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
There is not yet a consensus about the safety and efficacy of amlodipine in hypertensive crisis.• Pregnancy:
It is not advisable to start Angiotensin II Receptor Antagonists (AIIRAs) when pregnant. Patients who want to get pregnant should switch to other antihypertensive medications that have a proven safety record for use during pregnancy, unless ongoing AIIRA therapy is deemed necessary. AIIRAS treatment should be discontinued as soon as pregnancy is detected, and alternate therapy should be initiated if necessary.• Sodium-and/or volume-depleted patients:
In studies with a placebo, 0.4% of patients with simple hypertension receiving amlodipine + valsartan experienced excessive hypotension. Angiotensin receptor blockers may cause symptomatic hypotension in individuals with an active renin-angiotensin system (e.g., volume-and/or salt-depleted patients receiving high doses of diuretics). It is advised to treat this condition before starting Amlodipine + Valsartan or to begin treatment under close medical monitoring.In the event that Amlodipine + Valsartan causes hypotension, the patient should be put to sleep and, if required, given a normal saline intravenous infusion. After stabilising blood pressure, treatment can resume.
• Hyperkalemia:
It is advisable to use potassium supplements, potassium-sparing diuretics, potassium-containing salt replacements, and other medications that may raise potassium levels (heparin, etc.) concurrently with caution and frequent potassium level monitoring.• Renal artery stenosis:
When treating hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis to a single kidney, amlodipine plus valsartan should be used cautiously because these patients may experience an increase in blood urea and serum creatinine.
• Kidney Transplantation:
As of right now, there is no documented case of amlodipine plus valsartan being safely used in kidney transplant recipients.• Hepatic Impairment:
AmLODipine is not appropriate for patients with severe hepatic impairment. Caution should be exercised when administering Amlodipine + Valsartan to patients with hepatic impairment or biliary obstructive disorders in patients with mild to moderate hepatic impairment without cholestasis, the maximum recommended dose is 80mg valsartan. There is currently no established dosage for amlodipine in patients with mild to moderate hepatic impairment. When switching eligible hypertensive patients with hepatic impairment to amlodipine or Amlodipine + Valsartan, the lowest available dose of amlodipine monotherapy or of the amlodipine component, respectively, should be used. Renal impairment. No dosage adjustment of Amlodipine + Valsartan is required for patients with mild to moderate renal impairment (GFR >30 ml/min/1.73 m²).Patients wÃth moderate renal impairment should have their potassium and creatinine levels checked. This is especially important for those who are elderly or who have history of kidney disease.
• Primary Aldosteronism:
Patients with primary aldosteronism should not be treated with the angiotensin II antagonist valsartan because their renin-angiotensin system is affected by the primary disease.• Edema Angioedema:
Angioedema, consisting of swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue, has been reported in patients treated with valsartan. Some patients have previously experienced angioedema with other drugs, including ACE inhibitors. Amlodipine + Valsartan should be discontinued immediately in patients who develop angioedema and should not be restarted.• Heart failure/post-myocardial Infarction:
In susceptible individuals, alterations in kidney function may develop as a result of systemic renin-angiotensin-aldosterone inhibition. Patients with severe heart failure, whose kidneys are functioning may be dependent on the activity of the renin-angiotensin-aldosterone system, may experience oliguria, progressive azotemia, and (in rare cases) acute renal failure and/or death if they receive ACE inhibitors and angiotensin receptor antagonists. Valsartan has been associated with comparable outcomes. Evaluation of renal function is essential for patients suffering from myocardial infarction or heart failure.In a long-term placebo-controlled study (PRAISE-2) of amlodipine In NYHA patients (New York Heart Classification Association) Non-ischemic class III and IV heart failure, amlodipine was associated with an increase in cases of pulmonary edema although there was no significant difference in the incidence of heart failure more severe than placebo. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure because they may increase the risk of future cardiovascular events and death.
• Aortic and Mitral Valve Stenosis:
In a manner similar to all other vasodilators, patients with severe non-high grade aortic stenosis or mitral stenosis should use extra caution when using these medications.Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Co-administration of ACE inhibitors, ARBS, or aliskiren has been shown to raise the risk of hypotension, hyperkalemia, and reduced renal function, including acute renal failure.Therefore, dual blockade of the RAAS using a combination of ACE inhibitors, ARBS or aliskiren is not recommended.
if treatment with dual blockade is considered absolutely necessary then only should be performed under the supervision of a specialist and must closely and regularly monitor kidney function. function, electrolytes, and blood pressure. Patients with nephropathy associated with diabetes should not use ACE inhibitors and ARBS at the same time.
Other than hypertension, no patient population has been studied with amlodipine valsartan.
COMMERCE WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
Relations common to the combination
No medicine- medicine commerce studies have been other medicinal products.
To be taken into account with attendant use
performed with Amlodipine Valsartan and Other antihypertensive agents Generally used antihypertensive agents(e.g. nascence blockers, diuretics) and other medicinal products which may beget hypotensive adverse goods(e.g. tricyclic antidepressants, nascence blockers for treatment of benign prostate hyperplasia) may increase the antihypertensive effect of the combination.
Administration of amlodipine with grapefruit or grapefruit juice isn't recommended as bioavailability may be increased in some cases, performing in increased blood pressure lowering goods.
Caution needed with attendant use
CYP3A4 impediments attendant use of amlodipine with strong or moderate CYP3A4 impediments( protease impediments, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure. The clinical restatement of these pharmacokinetic variations may be more pronounced in the senior. Clinical monitoring and cure adaptation may therefore be needed.
CYP3A4 corrupters ( anticonvulsant agents (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, hypericum perforatum)
Uponco-administration of known corrupters of the CYP3A4, the tube attention of amlodipine may vary. thus, blood pressure should be covered and cure regulation considered both during and after attendant drug particularly with strong CYP3A4
corrupters (e.g. rifampicin, hypericum perforatum).
Simvastatin
Co-administration of multiple boluses of 10 mg amlodipine with 80 mg simvastatin redounded in a 77 increase in exposure to simvastatin compared to simvastatin alone. It's recommended to limit the cure of simvastatin to 20 mg daily in cases on amlodipine. Dantrolene( infusion)
In creatures, murderous ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to threat of hyperkalaemia, it's recommended that theco-administration of calcium channel blockers similar as amlodipine be avoided in cases susceptible to nasty hyperthermia and in the operation of nasty hyperthermia.
To be taken into account with attendant use Others
In clinical commerce studies, amlodipine didn't affect the pharmacokinetics of atorvastatin, digoxin, warfarin or ciclosporin.
relations linked to valsartan
attendant use is not recommended
Lithium
Reversible increases in serum lithium attention and toxin have been reported during attendant administration of lithium with angiotensin converting enzyme impediments or angiotensin II receptor antagonists, including valsartan. thus, careful monitoring of serum lithium situations is recommended during attendantuse. However, the threat of lithium toxin may presumably be increased further with Amlodipine/ Valsartan, If a diurectic is also used.
Potassium- sparing diuretics, potassium supplements, swab backups containing potassium and other substances that may increase potassiumlevels. However, monitoring of potassium tube situations is advised, If a medicinal product that affects potassium situations is to be specified in combination with valsartan.
Caution needed with attendant use Non-steroidalanti-inflammatory drugs ( NSAIDs), including picky COX- 2 impediments, acetylsalicylic acid(> 3 g/ day), andnon-selective NSAIDS
When angiotensin II antagonists are administered contemporaneously with NSAIDS attenuation of the antihypertensive effect may do likewise, attendant use of angiotensin II antagonists and NSAIDS may lead to an increased threat of worsening of renal function and an increase in serum potassium.
thus, monitoring of renal function at the morning of the treatment is recommended, as well as acceptable hydration of the case. Impediments of the uptake transporter( rifampicin, ciclosporin) or efflux transporter( ritonavir) The results of an in vitro study with mortal liver towel indicate that valsartan is a substrate of When Co-administrating valsartan with inhibitors of the hepatic uptake transporter OATP1B1 rifampicin, cyclosporine or efflux transporter MRP2 ritonavir, there may be an increase in systemic exposure to the drug. Binary leaguer of the RAAS with ARBS, ACE impediments or aliskiren.
Clinical trial data have shown that binary leaguer of the RAAS through the combined use of ACE impediments, ARBS or aliskiren is associated with a advanced frequence of adverse events similar as hypotension, hyperkalaemia and dropped renal function( including acute renal failure) compared to the use of a single RAAS- acting agent. Others In monotherapy with valsartan, no relations of clinical significance have been set up with the following substances cimetidine; warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipine, glibenclamide.
FERTILITY, PREGNANCY AND LACTATION
• Pregnancy
Amlodipine
It is unknown if amlodipine is safe to use during pregnancy in humans. Reproductive toxicity had been identified at excessive amounts in experiments on animals. Pregnancy ought to be administered with this medication if there is no other safe possibilities and the illness poses a higher danger to the mother and foetus.
Valsartan
Unfortunately, there is inconclusive epidemiological evidence on the risk of teratogenicity after taking exposure to ACE inhibitors in the first trimester of pregnancy, regardless of it is not acceptable to rule out a small amount increase in risk. Similar potential hazards might be applicable to this class of medications even though controlled epidemiological evidence on the risk with Angiotensin II Receptor Antagonists (AIIRAs) is lacking. Patients who are considering becoming pregnant should switch to other antihypertensive medications that have a proven safety record for use during pregnancy, unless ongoing AIIRA therapy is deemed necessary. When pregnancy is diagnosed, treatment with AlIRAS should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to AllRA therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to AllRAS have occurred from the second trimester of pregnancy. ultrasound check of renal function and skull is recommended. Infants whose mothers have taken AllRAS should be closely observed for hypotension.
• Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3-7%, with a maximum of 15%. The effect of amlodipine on infants is unknown. No information is available regarding the use of Amlodipine / Valsartan during breast-feeding; therefore Amlodipine / Valsartan is not recommended and alterative treatments with better established safety profiles during It is preferred to breastfeed, particularly when caring for a newborn or premature baby.• Fertility
There are no clinical trials on the use of amlodipine and valsartan together for fertility.At oral doses up to 200 mg/kg/day, valsartan exhibited no deleterious impact on the reproductive performance of either male or female rats. Based on a 60-kg patient and an oral dose of 320 mg/day, the calculations indicate that this amount is six times the maximum permissible human dose in milligrammes per millilitre.
Amlodipine
There have been reports of reversible biochemical modifications in the spermatozoa's head in certain patients who are using calcium channel blockers. There is not enough clinical evidence to determine whether amlodipine may affect fertility. Negative impacts on male fertility were discovered in a mouse study.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Patients utilising equipment or driving following the fact that taking Amlodipine/Valsartan should be aware that occasional restlessness or dizziness could appear. Amlodipine could possibly have a minimal to moderate adverse effect on one's capacity to operate machinery and drive. Reaction time may be compromised in amlodipine users who experience headaches, nausea, exhaustion, or dizziness.UNDESIRABLE EFFECTS
Summary of the Safety Profile
Five controlled clinical studies which might involve 5,175 patients—2,613 of whom received valsartan in addition to amlodipine—have assessed the safety of amlodipine/valsartan.• Nasopharyngitis,
• influenza,
• hypersensitivity,
• headache,
• syncope,
• orthostatic
• hypotension,
• oedema,
• pitting oedema,
• facial oedema,
• oedema peripheral,
• fatigue,
• flushing,
• asthenia,
• hot flush
were the adverse reactions the fact that were found to occur most frequently, significant, or severe.
Tabulated List of Rdverse Reactions
Adverse reactions have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (21/1,000 to <1/100): rare (21/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).Common
• Nasopharyngitis• Influenza
• Hypokalaemia
• Headache
• Asthenia
• Facial oedema
• Flushing
• hot flush
• Ankle swelling
• Fatigue.
Uncommon
• Anorexia• Hypercalcaemia
• Hyperlipidaemia
• Hyperuricemia
• Hyponatraemia
• Insomnia/sleep disorders
• Mood swings
• Depression
• Abnormal coordination
• Oedema peripheral
• Dizziness postural
• Paraesthesia
• Somnolence
• Syncope
• Tremor
• Hypoesthesia
• Visual impairment
• Vertigo
• Palpitations
• Tachycardia
• Orthostatic hypotension
• Cough
• Pharyngolaryngeal pain
• Abdominal discomfort
• abdominal pain upper
• Constipation
• Diarrhoea
• Dry mouth
• Nausea
• Dyspepsia
• Vomiting
• Alopecia
• Photosensitivity reaction
• Rash, Arthralgia
• Back pain
• Joint swelling
• Skin discolouration
• Myalgia
• Micturition disorder
• Nocturia
• Discomfort
• malaise
• Impotence
• Non cardiac chest Pain
• Dyspnoea
• Rhinitis
• Weight decrease/increase
• Gynaecomastia,
Rare
• Hypersensitivity• Anxiety
• Visual disturbance
• Tinnitus, Syncope
• Hypotension
• Exanthema
• Hyperhidrosis
• Pruritus
• Muscle spasm
• Sensation of heaviness
• Pollakiuria
• Polyuria, Erectile dysfunction
• Confusion
Very Rare
• Leukopenia• Thrombocytopenia sometimes with purpura
• Hyperglycaemia
• Hypertonia
• Peripheral neuropathy
• neuropathy
• Arrhythmias
• Myocardial infarction
• Vasculitis
• Gastritis
• Gingival hyperplasia
• Pancreatitis
• Hepatitis
• Intrahepatic Cholestasis
• Jaundice
• Urticaria
• Exfoliative dermatitis
• Stevens-Johnson syndrome
• Erythema multiforme
• Angioedema
Not Known
• Haemoglobin and haematocrit decreased• Neutropenia
• Extrapyramidal syndrome
• Dermatitis bullous
• Toxic Epidermal Necrolysis
• Blood potassium increased
Reporting of suspected adverse reactions
Reporting any potential adverse reactions as soon as the prescription has been approved is crucial. It enables continuous monitoring of the benefit/risk ratio of the drug.OVERDOSE:
Symptoms
No overdose with Amlodipine + Valsartan has ever been reported. Significant hypotension combined with vertigo may be the primary indicator of a valsartan overdose. Severe peripheral vasodilation and reflex tachycardia are possible side effects of amlodipine overdose. Significant and perhaps long-lasting systemic hypotension that results in shock and mortality has been reported.
Treatment
If ingestion occurred recently, stomach lavage or induction of vomiting may be considered. It has been shown that giving activated charcoal to healthy individuals as soon as they take amlodipine or up to two hours later significantly decreases the medication's absorption.Active cardiovascular support is necessary in cases of clinically substantial hypotension brought on by an overdose of amlodipine and valsartan. This care should include regular monitoring of respiratory and cardiac functions, elevation of the extremities, and attention to urine output and circulating fluid volume.
Restoring normal blood pressure and vascular tone may involve the use of a vasoconstrictor. If there is no reason not to use it, then it is not contraindicated. Intravenous calcium gluconate has the potential to counteract the effects of calcium channel blockage. Amlodipine and valsartan are unlikely to be eliminated by hemodialysis.
PRECLINICAL SAFETY DATA Amlodipine+Valsartan
The following adverse responses were noted in animal experiments that may have clinical significance:Histopathological signs of inflammation of the glandular stomach were seen in male rats at an exposure of about 1.9 (valsartan) and 2.6 (amlodipine) times the clinical doses of 160mg valsartan and 10 mg amlodipine. Both males and females experienced erosion of the stomach mucosa and ulcers at greater exposure levels. Similar changes were also seen in the valsartan alone group (exposure 8.5-11.0 times the clinical dose of 160mg-valsartan).
When renal tubular basophilia/hyalinization, dilation, and casts were exposed at 8–13 (valsartan) and 7-8 (amlodipine) times the clinical doses of 160 mg valsartan and 10 mg amlodipine, there was also an increased incidence and severity of these side effects. The group that received valsartan alone (exposure 8.5–11.0 times the clinical dose of 160 mg valsartan) experienced similar alterations.
In an embryo-foetal development study in the rat, increased incidences of dilated ureters, malformed stemnebrae, and unossified forepaw phalanges were noticed at exposures of about 12 (valsartan) and 10 (amlodipine) times the clinical doses of 160mg valsartan and 10 mg amlodipine. Dilated ureters were also found in the valsartan alone group (exposure 12 times the clinical dose of 160mg valsartan). In this investigation, there were only mild indications of maternal toxicity (moderate body weight loss). Based on AUC, the no-observed-effect-level for developmental impacts was found at three folds for valsartan and four folds for amlodipine after clinical exposure.
There was no proof that the single chemicals were carcinogenic, clastogenic, or mutagenic.
Extor Tablet Latest Price in Pakistan
✓ Extor 5mg+80mg Tablets are available in an alu-alu blister pack of 14 Tablets and price is RS:345
✓ Extor 5mg 160mg Tablets are available in alu-alu blister pack of 14 Tablets and price is RS:445
✓ Extor 10mg+160mg Tablets are available in alu-alu blister pack of 14 Tablets and price is RS:505
Manufactured by:
The Searle Company Limited, 32-Km, Multan Road, Lahore-Pakistan.
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