caduet tablets Uses, Dosage, Side Effects, Precautions & Warnings

caduet Generic drug of the Therapeutic class: Cardiology and angiology
Active ingredients: Amlodipine , Atorvastatin

what is caduet medication?

• This medication is supplied as blue, oval-shaped, film-coated tablets debossed with “Pfizer” on one side and “CDT 101” on the other side.
• Boxes of 7, 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 or 200 tablets.
• Not all presentations may be marketed.

what is caduet medication used for and   indication?

• CADUET is indicated for the prevention of cardiovascular events in hypertensive patients with 3 associated cardiovascular risk factors, with normal to moderately elevated cholesterol without established coronary artery disease, and in whom, according to current recommendations, the concomitant use of amlodipine and a low dose of atorvastatin is suitable .
• CADUET should be used when the response to regimen and other non-pharmacological measures is inadequate.

caduet dosage

Oral route

• The usual starting dose is 5 mg / 10 mg once daily.
• If tighter blood pressure control is required, a dosage of 10 mg / 10 mg once daily may be administered.
• The tablets can be taken at any time of the day, with or without food.
• CADUET can be used alone or in combination with other antihypertensive drugs, but it must not be used in combination with other calcium channel blockers or another statin.
• The combination of CADUET and fibrates should generally be avoided (see sections 4.4 and Interactions with other medicinal products and other forms of interaction ).

Patients with renal impairment : No dosage adjustment is necessary in patients with impaired renal function (see sections 4.4 and Pharmacokinetic properties ).

Patients with hepatic impairment : CADUET is contraindicated in patients with active hepatic disease.

Children / Adolescents : The safety and efficacy of CADUET have not been established in children / adolescents. Therefore, the use of CADUET is not recommended in this population.

Elderly : It does not appear necessary to adjust the dose in the elderly (see section Pharmacokinetic properties ).

Combination with other medicinal products : In combination with ciclosporin, the dose of atorvastatin should not exceed 10 mg (see section Interactions with other medicinal products and other forms of interaction ).

Contraindications

CADUET is contraindicated in patients:

• Being hypersensitive to dihydropyridines *, to amlodipine, to atorvastatin or to any of the excipients of this medicine,
• have active liver disease or a persistent and unexplained increase in serum transaminases exceeding 3 times the upper limit of normal,

In women who are pregnant, breastfeeding or of childbearing potential and not using reliable contraceptive methods (see section Pregnancy and breast-feeding ),

In combination with itraconazole, ketoconazole, telithromycin (see section Interactions with other medicinal products and other forms of interactions ),

having severe hypotension,

Having shock (including cardiogenic shock),

Having an obstruction of the efferent pathway to the left ventricle (for example severe aortic stenosis),

With haemodynamically unstable heart failure after acute myocardial infarction.

* amlodipine is a calcium channel blocker derived from dihydropyridine.

HOW TO TAKE CADUET?

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if in doubt.

Adults

• The recommended starting dose of CADUET is one 5 mg / 10 mg tablet per day. Your doctor may increase the dose if necessary to 1 tablet of CADUET 10 mg / 10 mg per day.
• The tablets should be swallowed whole with a glass of water. They can be taken at any time of the day, with or without food. However, it is best to take them at the same time each day.
• Continue to follow your doctor’s dietary advice, especially to eat a low fat diet, avoid tobacco, and exercise regularly.
• If you have the impression that the effect of CADUET tablets is too strong or too weak, talk to your doctor or pharmacist.

Use in children and adolescents

• This medication is not recommended for children and adolescents.

If you take more CADUET 10 mg / 10 mg film-coated tablets than you should

If you accidentally take too many CADUET tablets (more than your usual dose), ask your doctor or the nearest hospital for advice. Take any remaining tablets, the carton or the whole carton with you so that hospital staff can quickly identify which medicine you have taken.

If you forget to take CADUET 10 mg / 10 mg film-coated tablets

If you forget to take your dose of CADUET, take your next dose at the normal time.

Do not take a double dose to make up for the dose you forgot to take.

If you stop taking CADUET 10 mg / 10 mg film-coated tablets

Do not stop taking CADUET unless your doctor tells you to.

If you have any further questions on the use of this medicine or want to stop taking your treatment, ask your doctor or pharmacist for more information.

How To Store Caduet?

• Keep this medication out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the blister, the carton and the vial after “EXP”. The expiration date refers to the last day of that month.
• Store at a temperature not exceeding 30 ° C.
• Do not throw away any medicines via a wastewater treatment plant or with household waste. Ask your pharmacist how to throw away the medicines you no longer use. These measures will help protect the environment.

caduet side effects

• The safety of CADUET has been evaluated in double-blind, placebo-controlled studies in 1092 patients treated for concomitant hypertension and dyslipidemia. During clinical trials with CADUET, no specific adverse events specific to this combination were observed.
• Adverse events were limited to those previously reported for amlodipine and / or atorvastatin (see table of adverse events below).
• In controlled clinical trials, discontinuation of treatment due to clinical adverse events or laboratory abnormalities was observed in 5.1% of patients treated with amlodipine and atorvastatin versus 4.0% of patients treated with amlodipine and atorvastatin. patients taking a placebo.
• The adverse events below, listed according to MedDRA system organ classification and frequency order, relate to amlodipine and atorvastatin individually.
• Very common: ³ 1/10, common: ³ 1/100 and <1/10, infrequent: ³ 1/1000 and <1/100, rare: ³ 1/10000 and <1/1000, very rare: < 1 / 10,000, frequency not known (cannot be estimated from the available data).

MedDRA System organ classes	Side effects	Frequency
		Amlodipine	Atorvastatin
Infections and infestations	Nasopharyngitis	–	Frequent
Blood and lymphatic system disorders	Leukopenia	Very rare	–
	Thrombocytopenia	Very rare	Rare
Immune system disorders	hypersensitivity	Very rare	Frequent
	Anaphylaxis	–	Very rare
Metabolism and nutrition disorders	Hyperglycemia *	Very rare	Frequent
	Weight gain	Infrequent	Infrequent
	Weightloss	Infrequent	–
	Hypoglycemia	–	Infrequent
	Anorexia	–	Infrequent
Psychiatric disorders	Insomnia	Infrequent	Infrequent
	Mood disorders (including anxiety)	Infrequent	–
	Nightmares	–	Infrequent
	Depression	Infrequent	Frequency not known
	Confusion	Rare	–
Disorders of the system nervous	Drowsiness	Frequent	–
	Dizziness	Frequent	Infrequent
	Headache (especially at the start of treatment)	Frequent	Frequent
	Tremors	Infrequent	–
	Hypoesthesias, paresthesias	Infrequent	Infrequent
	Syncope	Infrequent
	Hypertonia	Very rare	–
	Peripheral neuropathy	Very rare	Rare
	Amnesia	–	Infrequent
	Dysgeusia	Infrequent	Infrequent
	Extrapyramidal syndrome	Frequency not known	–
Eye disorders	Blurred vision	–	Infrequent
	Visual disturbances (including diplopia)	Infrequent	Rare
Ear and labyrinth disease	Tinnitus	Infrequent	Infrequent
	Hearing loss	–	Very rare
Cardiac disorders	Palpitations	Frequent	–
	Angina pectoris	Rare	–
	Myocardial infarction	Very rare	–
	Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation)	Very rare	–
Vascular disorders	Flushing	Frequent	–
	Hypotension	Infrequent	–
	Vasculitis	Very rare	–
Respiratory, thoracic and mediastinal disorders	Pharyngolaryngeal pain	–	Frequent
	Epistaxis	–	Frequent
	Dyspnea	Infrequent	–
	Rhinitis	Infrequent	–
	Cough	Very rare	–
	Interstitial lung disease, especially during long-term treatment		Frequency not known
Gastrointestinal disorders	Gingival hyperplasia	Very rare	–
	Nausea	Frequent	Frequent
	Upper and lower abdominal pain	Frequent	Infrequent
	Vomiting	Infrequent	Infrequent
	Dyspepsia	Infrequent	Frequent
	Changes in intestinal transit (including diarrhea and constipation)	Infrequent	–
	Dry mouth	Infrequent	–
	Dysgeusia	Infrequent	–
	Diarrhea, constipation, gas	–	Frequent
	Gastritis	Very rare	–
	Pancreatitis	Very rare	Infrequent
	Eructation	–	Infrequent
Hepatobiliary disorders	Hepatitis	Very rare	Infrequent
	Cholestasis	–	Rare
	Jaundice	Very rare	–
	Hepatic insufficiency	–	Very rare
Skin and subcutaneous tissue disorders	Bullous dermatosis including erythema multiforme	Very rare	Rare
	Angioedema	Very rare	–
	Erythema multiforme	Very rare	–
	Alopecia	Infrequent	Infrequent
	Purpura	Infrequent	–
	Skin discoloration	Infrequent	–
	Pruritus	Infrequent	Infrequent
	Eruption	Infrequent	Infrequent
	Hyperhidrosis	Infrequent	–
	Exanthema	Infrequent	–
	Urticaria	Very rare	Infrequent
	Angioneurotic edema	Very rare	Rare
	Exfoliative dermatitis	Very rare	–
	Photosensitivity	Very rare	–
	Stevens-Johnson syndrome	Very rare	Rare
	Bullous erythroderma with epidermolysis	–	Rare
Musculoskeletal and connective tissue disorders	Swelling of the joints (including swelling of the ankles)	Frequent	Frequent
	Arthralgia, myalgia (see section Warnings and precautions for use )	Infrequent	Frequent
	Muscle cramps, muscle spasms	Infrequent	Frequent
	Back pain	Infrequent	Frequent
	Neck pain	–	Infrequent
	Pain in extremity	–	Frequent
	Muscle fatigue	–	Infrequent
	Myositis (see section Warnings and precautions for use )	–	Rare
	Rhabdomyolysis, myopathy (see section Warnings and precautions for use )	–	Rare
	Tendinopathies, in rare cases tendon rupture	–	Rare
	Immune-mediated necrotizing myopathy	–	Frequency not known
Kidney and urinary tract disorders	Urination disorder, nocturia, pollakiuria	Infrequent	–
Reproductive system and breast disorders	Incapacity	Infrequent	Infrequent
	Gynecomastia	Infrequent	Very rare
General disorders and administration site conditions	Edema	Frequent	Infrequent
	Peripheral edema	–	Infrequent
	Tired	Frequent	Infrequent
	Chest pain	Infrequent	Infrequent
	Asthenia	Infrequent	Infrequent
	Pain	Infrequent	–
	Discomfort	Infrequent	Infrequent
	Fever	–	Infrequent
Investigations	Increased liver enzymes: alanine aminotransferase, aspartate aminotransferase (mainly related to cholestasis)	Very rare	Frequent
	Blood CK increased (see section 4.4 )	–	Frequent
	Leukocyturia	–	Infrequent

* Diabetes: The frequency depends on the presence or absence of risk factors (fasting blood sugar ³ 5.6 mmol / l, BMI> 30 kg / m², increased triglyceride levels, history of high blood pressure).

caduet Interactions

Taking other medications

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Some medicines may interact with CADUET 10 mg / 10 mg film-coated tablets. This interaction may cause one or both of the medicines to be less effective, or on the contrary, this interaction may increase the risk or severity of side effects, including major muscle disorders known as rhabdomyolysis and myopathy (see section 4). .

Some medicines may interact with CADUET 10 mg / 10 mg film-coated tablets:

• certain antibiotics such as rifampicin or certain “macrolide” antibiotics such as erythromycin, clarithromycin, telithromycin, fusidic acid or certain drugs used to treat infections caused by fungi such as ketoconazole, itraconazole,
• medicines used to regulate lipid levels: fibrates, such as gemfibrozil or colestipol,
• medicines used to regulate your heart rhythm, such as amiodarone, diltiazem and verapamil,
• medicines used to treat or prevent seizures such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
• medicines used to change how your immune system works, such as cyclosporin
• protease inhibitors such as ritonavir, indinavir, nelfinavir used in the treatment of HIV,
• medicines used to treat depression, such as nefazodone and imipramine,
• medicines used to treat mental disorders, such as neuroleptics,
• medicines used to treat heart failure, such as beta blockers
• medicines used to treat high blood pressure, such as angiotensin II inhibitors, converting enzyme inhibitors, verapamil and diuretics,
• alpha blockers used to treat high blood pressure or prostate problems
• other medicines known to interact with CADUET 10 mg / 10 mg film-coated tablets such as ezetimibe (which lowers cholesterol), warfarin (which decreases blood clotting), oral contraceptives, stiripentol (an anticonvulsant used for treatment of epilepsy), cimetidine (used for heartburn and stomach ulcers), phenazone (a pain reliever), antacids (containing aluminum or magnesium, used to relieve problems stomach), and amifostine (used to treat cancer),
• sildenafil (used in the treatment of erectile dysfunction, impotence),
• dantrolene and baclofen (muscle relaxants),
• steroids,
• over-the-counter St. John’s Wort products.

CADUET may lower your blood pressure further if you are already taking other medicines to treat your high blood pressure.

If you are taking or have recently taken any other medicines, including medicines obtained without a prescription, talk to your doctor or pharmacist.

INTERACTIONS OF CADUET 10 MG / 10 MG WITH FOOD AND DRINK

Food and drinks

• CADUET 10 mg / 10 mg film-coated tablets can be taken at any time of the day, with or without food.

Grapefruit juice

• Do not take more than one or two glasses of grapefruit juice per day as large amounts of grapefruit juice may affect the effects of CADUET 10 mg / 10 mg film-coated tablets.

Alcohol

• Avoid drinking too much alcohol while taking CADUET 10 mg / 10 mg film-coated tablets. See also section 2 “Take special care with CADUET 10 mg / 10 mg film-coated tablets” for more details.

Drive and use machines

Do not drive or use machines if you feel dizzy after taking this medicine.

Warnings and Precautions

Heart failure

• Patients with heart failure should be treated with caution. In a long-term placebo-controlled study in patients with severe heart failure (NYHA class III and IV), the reported incidence of pulmonary edema was higher in the amlodipine group compared to the placebo group. (see section Pharmacodynamic properties). Calcium channel blockers including amlodipine should be used with caution in patients with congestive heart failure because they may increase the risk of cardiovascular events and mortality.

Liver effects

• Liver function tests should be performed before the start of treatment and then regularly after initiation of treatment, as well as in the event of signs or symptoms suggestive of liver damage. In the event of elevation of the serum transaminase level, monitoring is necessary until normalization.
• A persistent increase in ALT or AST exceeding 3 times the upper limit of normal (ULN), should lead to discontinuation of treatment.
• The half-life of amlodipine is increased and its AUC (Area Under the Curve) is greater in patients with hepatic impairment; dosage recommendations have not been established.
• Due to the presence of atorvastatin, CADUET should be used with caution in patients who consume large amounts of alcohol, in patients with hepatic impairment and / or a history of liver disease.

Muscle effects

• Like other HMG-CoA reductase inhibitors, atorvastatin can affect skeletal muscles and lead to myalgia, myositis and myopathies. These muscle damage may rarely progress to rhabdomyolysis, characterized by high levels of creatine kinase (CK) (more than 10 times the ULN), myoglobinemia and myoglobinuria which can lead to kidney failure, and in some cases be fatal.
• Regular testing of CK or other muscle enzymes is not recommended in asymptomatic patients treated with statins. However, dosing of CKs is recommended before initiating statin therapy in patients with predisposing factors to rhabdomyolysis as well as in those with muscle symptoms during statin therapy (see below).
• Very rare cases of autoimmune-mediated necrotizing myopathies (IMNM) have been reported during or after treatment with certain statins. IMNM is clinically characterized by proximal muscle weakness and increased serum creatine kinase, which persist despite discontinuation of statin therapy.

Before initiation of treatment

• CADUET should be prescribed with caution in patients with predisposing factors to rhabdomyolysis. Before starting treatment with a statin, creatine kinase (CK) levels should be checked in the following situations:
  • Renal failure.
  • Hypothyroidism.
  • Personal or family history of genetic muscle diseases.
  • Personal history of muscle toxicity during treatment with a statin or a fibrate.
  • History of liver disease and / or excessive alcohol consumption.
• In elderly patients (> 70 years), the need for these measures should be assessed, depending on the presence of other factors predisposing to rhabdomyolysis.
• Situations in which increased plasma concentrations may occur, due to interactions (see section 4.5) and use in special populations including genetic polymorphisms (see section 5.2). ).
• In these situations, a regular reassessment of the benefit / risk of the treatment, as well as regular clinical monitoring is recommended.
• If the initial CK level is significantly elevated (more than 5 times the ULN) treatment should not be started.

Creatine kinase measurement

• Creatine kinase (CK) should not be measured after heavy exercise or in the presence of another possible cause of increased CK, as this will make interpretation of the results difficult. In the event of a significant elevation of CK (more than 5 times the ULN) before treatment, this should be systematically checked again within 5 to 7 days to confirm the results.

During treatment

• It is recommended that patients be asked to promptly report any unexplained muscle pain, muscle cramps or weakness, particularly if accompanied by malaise or fever.
• · If symptoms appear when a patient is under treatment with CADUET, a CK levels should be measured; if the CK level is significantly elevated (more than 5 times the ULN), treatment should be discontinued.
• · If muscular symptoms are severe and cause daily discomfort, discontinuation of treatment should be considered, even if CK levels did not exceed 5 times the ULN.
• · If symptoms resolve and CK levels return to normal, the reintroduction of CADUET may be considered at the lowest dose and under close supervision.
• Treatment with CADUET should be discontinued in the event of a clinically significant increase in CK level (> 10 times the ULN) or if rhabdomyolysis is diagnosed or suspected.
• Amlodipine has no effect on laboratory parameters.

Combinations with other drugs

• As with other statins, the risk of rhabdomyolysis is increased when CADUET is administered in combination with certain drugs which may increase the plasma concentration of atorvastatin, such as strong inhibitors of CYP3A4 or protein transporters (eg, cyclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, determovir and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir, etc / ritonavir). The risk of myopathy may also be increased in combination with gemfibrozil and other fibrates, antivirals used in the treatment of hepatitis C (HCV) (boceprevir, telaprevir, elbasvir / grazoprevir), erythromycin, niacin, l ‘ ezetimibe or colchicine. Therapeutic alternatives (not exhibiting these interactions) should be considered as far as possible.
• In the event that the combination of these medicinal products with CADUET is necessary, the benefit / risk of concomitant treatments should be carefully assessed and appropriate clinical monitoring is recommended (see section Interactions with other medicinal products and other forms of interactions).
• CADUET should not be administered simultaneously with fusidic acid in systemic form, and for up to 7 days after stopping treatment with fusidic acid. In patients where the use of systemic fusidic acid is considered essential, statin therapy should be discontinued for the duration of fusidic acid therapy. Cases of rhabdomyolysis (some fatal) have been reported in patients receiving fusidic acid and a statin in combination (see section Interactions with other medicinal products and other forms of interactions). Patients should be informed of the need to seek immediate medical attention if they experience symptoms of muscle weakness, pain, or muscle tenderness.
• Statin therapy can be restarted seven days after the last dose of fusidic acid.
• In exceptional circumstances, when prolonged treatment with systemic fusidic acid is required, e.g. for the treatment of severe infections, the need for co-administration of CADUET and fusidic acid should only be considered in cases of per case and under close medical supervision.

Prevention of stroke by aggressively lowering cholesterol levels (SPARCL study)

• In a posteriori analysis performed in subgroups of patients with recent stroke or transient ischemic attack (TIA) but without coronary artery disease, a higher frequency of hemorrhagic stroke was observed in treated patients. per 80 mg atorvastatin compared to patients on placebo.
• This high risk is particularly observed in patients who have already had a hemorrhagic stroke or a lacunar infarction at the inclusion of the study.
• In patients with a history of hemorrhagic stroke or lacunar infarction, the benefit / risk balance of atorvastatin 80 mg is uncertain. Therefore, the potential risk of occurrence of haemorrhagic stroke should be carefully assessed before any initiation of treatment (see section Pharmacodynamic properties).

Interstitial lung disease

• Cases of interstitial lung disease have exceptionally been reported with certain statins, particularly during long-term therapy .
• Symptoms may include dyspnea, a non-productive cough, and altered general condition (fatigue, weight loss, and fever). If interstitial lung disease is suspected in a patient, statin therapy should be discontinued.

Diabetes

• There is some evidence that statins, as a pharmacological class, increase blood sugar. In some patients at high risk of developing diabetes, statins may cause hyperglycaemia requiring the initiation of diabetes treatment. This risk is nevertheless compensated by the reduction in the vascular risk under statins and therefore it should not be a reason for stopping statins. Patients at risk (fasting blood glucose between 5.6 and 6.9 mmol / l, BMI> 30 kg / m², increased triglyceride levels, arterial hypertension) should be monitored clinically and biologically in accordance with national recommendations.

PREGNANCY & BREAST-FEEDING & FERTILITY

Caduet is contraindicated during pregnancy and lactation.

Women of childbearing age

Women of childbearing potential should use reliable contraceptive measures during treatment ( see Contraindications ).

Pregnancy

Reversible biochemical changes in the sperm head have been reported in some patients treated with calcium channel blockers. There is insufficient clinical data regarding the potential effect of amlodipine on fertility. In a study carried out in rats, adverse effects were detected on male fertility ( see Preclinical safety ).

What happens if I overdose from Caduet?

No information is available regarding overdose of Caduet in humans.

What should I do if I miss a dose?

If you forget to take CADUET 5/ 10 mg -5/ 10 mg film-coated tablets:

• If you forget to take your dose of CADUET, take your next dose at the normal time.
• Do not take a double dose to make up for the dose you forgot to take.

What is  Forms and Composition ?

5 mg / 10 mg film-coated tablet (oval, debossed with “Pfizer” on one side and “CDT 051” on the other side; white) and 10 mg / 10 mg (oval, debossed with “Pfizer “On one side and” CDT 101 “on the other side; blue):   Boxes of 30 and 90, in blisters.

Excipients (common): Core: calcium carbonate, croscarmellose sodium, microcrystalline cellulose, pregelatinized corn starch, polysorbate 80, hydroxypropylcellulose, colloidal anhydrous silica, magnesium stearate. Film- coating : 5 mg / 10 mg tablet: Opadry II white 85F28751 (polyvinyl alcohol, titanium dioxide E171, macrogol 3000, talc). 10 mg / 10 mg tablet: Opadry II blue 85F10919 (polyvinyl alcohol, titanium dioxide E171, macrogol 3000, talc, indigo carmine aluminum lake E132).