10/10 ATORVA PLUS

10/10 ATORVA PLUS
20 May

10/10 ATORVA PLUS

Cholesterol Reducers And Hypolipidemic

- Atorvastatin is a selective competitive inhibitor of HMG – COA reductase which is the rate - limiting 
 enzyme responsible for conversion of (HMG – COA) to Mevalonate, a precursor of sterols including  
 cholesterol.
- Atorvastatin is rapidly absorbed after oral administration , plasma concentrations(Cmax) occure 
 within 1-2 hours 
- More than 98% of Atorvastatin is bond to plasma proteins. 
- Atorvastatin undergoes an extensive metabolism to active ortho and para metabolites hydroxylated 
 which 70% of circulatory inhibitory activity of HMG -COA reductase is attributed to active 
 metabolites .
- Atorvastatin is eliminated primarily in bile following hepatic and / or extrahepatic metabolism.
- Mean plasma elimination half – life of Atorvastatin in humans is approximately 14 hours.    
- The half life of inhibotry activity for HMG-COA reductase is approximately 20-30 hours due to the 
 contribution of active metabolites. 
- Ezetimibe is a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of 
 cholesterol and related phytosterols.
- Ezetimibe is absorbed and extensively conjugated to pharmacologically Active phenolic glucoronide 
 (Ezetimibe glucoronide).
- Ezetimibe and Ezetimibe glucoronide are highly bound (90 %) to human plasma proteins.
- Ezetimibe is primary metabolized in small intestinal and liver via glucoronide conjugation with  
 subsequent billary and renal excretion.

Indecation

- Atorva®plus is indicated as an adjunct to diet for reduction elevated cholesterol and triglyceride 
 values, when response to diet and other non pharmacological measures (such as :- physical exercises , 
 weight loss) is inadequate in patient with :-
- Elevated' Total cholesterol, LDL-cholesterol, apoliprotein B.
-Elevated triglycerides in patieat with primary hypercholesterolemia including familial 
 hypercholesterolaemia , or Mixed hyperlipidaemia.

Dosage & Administration

 The patient Should be placed on Standared Cholesterol lowering diet before receiving Atorva®plus 
 and Should continue on this diet during treatment with Atorva®plus. 
- Hypercholesterolaemia (Heterozygous Familial and Nonfamilial) and mixed dyslipidemia. The 
 therapy should be initiated at adose of 10 mg daily. The dosage range is 10 to 80 mg once daily.  
 Atorvastatin can be administrated as single dose at any time of the day with or without food.
 Individualisation, of the therapy should be done according to goal of therapy and response lipid levels 
 should be analysed within 2-4 weeks of initiation of therapy and / or dose escalation and the dosage 
 adjusted accordingly.      The LDL-C levels should be used to initiate and assess the treatment 
 response. If LDL-C values are unavailable then total-C values can be used to monitor therapy.
 Homozygous Familial Hypercholesterolaemia:Atorvastatin should be used as adjunct to other 
 lipid-lowering treatment (e.g. LDL apheresis) in these patients or if such treatments are unavailable.   
 The recommended dose is 10 to 80 mg daily concomitant Lipid-Lowering Therapy:   
- Ezetimibe can be administered with Atorvastatin (in patients with primary hyperlipidemia). For  
 convenience, the daily dose of Ezetimibe can taken at the same time as the Atorvastatin or fenofibrate,  
 according to the dosing recommendations for the respective medications. 
- Patients with renal insufficiency: 
  No dosage adjustment are required
- Patients with hepatic insufficiency:
 Atorvastatin: Exposure to the drug is greatly increased moderate to sever hepatic dysfunction, so 
 caution should be taken in patients who consume substantial quantities of alcohol and/or have a 
 history of  liver disease.
 Ezetimibe: No dosage adjustment is necessary in patients with mild hepatic impairment.
 Geriatric Patients Ezetimibe: No dosage adjustment is necessary in geriatric patients. 

 Each film coated tablet  contains:
 Atorvastatin ( As  Atorvastatin Calcium trihydrate)             10 mg        
 Ezetimibe                                                                              10 mg

- Atorva®plus is Contraindicated in patients with :-
- Hypersensitivity to any component of this medication.
-Liver disease or unexplained elevations, of hepatic function test values (Serum transaminases).
-Skeletal muscle disease 

 The risk of myopathy during treatment with HMG-COA reductase inhibitors is increased with 
 concurrent administration of cyclosporine, fibric acid derivatives, macrolide antibiotics including 
 erythromycin, azole antifungals or niacin and on rare occasions has resulted in rhabdomyolysis with 
 renal dysfunetion Secondary to Myoglobinuria. 
- Concurent use of Atorvastatin and digoxin may increase digoxin Serum Concentrations in large dose .
- Concurent use of Atorvastatin and Colestipol decrease plasma   Concentration of Atorvastatin .
- Coadministration of Atorvastatin with oral Contraceptives produce increases in plasma concentrations 
 of norethindrone and ethinyloestradiol .  
- Coadministration of Atorvastatin with an oral antacid Suspension containing magnesium and 
 aluminium hydroxides decreased plasma concentrations of Atorvastatin.
- Concurrents use of Atorvastatin with grapefruit juice Can increase plasma Concentrations of  
 Atorvastatin Since grapefruit juice contains one or more components that inhibit CYP3A4 
 concomitant intake of large quantities of grapefruit juice and Atorvastatin is therefore not 
 recommended .
-Inhibitors of cytochrom P450  3A4: (e.g : ciclosporn, macrolide antibiotics including erythromycin 
 and Clarithromycin, nefazodone,azole antifungals including itraconazole and HIV protease inhibitors), 
 concomitant administration can lead to increased plasma concentration of Atorvastatin .
- Inhibitors of P-glycoprotein :( e.g : ciclosporn) can increased the bioavailability of Atorvastatin.
- Protease inhibitors: coadministration of Atorvastatin with protease inhibitors was associated with 
 increase the bioavailability of Atorvastatin.
- Gemfibrozil/ fibric acid derivatives: the risk of Atorvastatin - induced myopathy may be increased.
-Warfarin: coadministration of Atorvastatin and warfarin caused a small decrease in brothrompin time 
 in the first days and become normal within 15 days of Atorva®plus treatment.
- phenazone: coadministration of multiple doses of Atorva®plus and phenazone should little or no 
 detectable effect in the clearance of phenazone.
 Cyclosporine: caution Should be exercised when  Ezetimibe and Cyclosporine used together due to 
 increase exposure to both Ezetimibe and Cyclosporine. 

-Atorva®plus is Contraindicated in Pregnancy and while breast Feeding: Women of child – bearing 
 potential should use appropriate contraceptive measures. 
 It is unknown whether this drug or its metabolites are excreted in human milk .

 Atorva®plus contains two substances: Atorvastatin and Ezetimibe. 
 Atorvastatin is generally well tolerated , the adverse effects observed are usually mild and transient 
*Gastrointestinal disorders:Common: constipation, flatulence, dyspepsia, nausea, diarrhea.
 Uncommon: anorexia, vomiting.
 Immune system disorders :
 Rare         : anaphylactic / anaphylactoid reaction .
 Psychiatric disorders:
 Rare           : Mood disorders, insomnia and nightmares.
 Nervous system disorders:
 Common   : light –headedness , headache .
 Uncommon : vertigo, tinnitus, drowsiness .
 Rare            : Confusion .  
 Eye disorders :
 Rare               : Conjunctivitis , Visual disturbances including blurred  vision .
 Cardiac disorders :
 Uncommon : Palpitations. 
 Blood and lymphatic system disorders:Uncommon: thrombocytopenia.
 Immune system disorders:Common: allergic reaction.
 Very rare: anaphylaxis.
 Endocrine disorders:Uncommon: alopecia, hypoglycemia, pancreatitis.
 Psychiatric:Common: insomnia.
 Uncommon: amnesia.
 Nervous system disorders:Common: headache, dizziness, paraesthaesia, hypoesthesia.
 Uncommon: peripheral neuropathy.
 Hepato-biliary disorders: Rare: hepatitis, cholestatic jaundice.
 Skin/appendages:Common: skin rash, pruritus.
 Uncommon: urticaria.
 Very rare: angioneurotic oedema, bullous rashes (including erthema multiforme, stevens-Johnson  
 syndrome and 
 toxic epidermal necrolysis).  
 Ear and labyrinth disorders:Uncommon: tinnitus.
 Musculoskeletal disorders:Common: myalgia, erthralgia.
 Uncommon: myopathy.
 Rare: myositis, rhabdomyolysis.
 Reproductive system disorders:Uncommon: impotence.
 General disorders:Common: asthenia, chest pain, peripheral oedema.
 Uncommon: malaise, weight gain.
 The must common adverse reaction in the group of patients treated with Ezetimibe & Atorvastatin that 
 lead to treatment discontinuation and occur at a rate greater than Atorvastatin alon were:
•    Alanine aminotransferase increase (0.6%).
•     Myalgia (0.5%).
•    Fatigue, aspartate aminotransferase increase headache. 
Over dose :
 INo specific treatment is available for Atorva®plus over dosage. When overdose occurs, the patient 
 should be treated symptomatically and supportive measures instated as required. Liver function tests 
 should be performed and serum CPK levels should be monitored.
 

    *liver effects:-
- liver function Should be tested prior the initiation of therapy and at 12 weak  following initiation of 
 therapy.
- Patients who develop increased  transaminase  levels  should be monitored until  the abnormalities 
 resolve .
 If the liver function  values should increase to more than triple the normal level and persist over longer 
 period , dose reduction or  withdrawal of Atrovastatin  is recommended .
   *Skeletal muscle effects :-
 Atorvastatin may in rare occasion affect the skeletal muscel and cause myalgia , myositis and myopthy .   
 The increasea of muscle enzyme (CPK) in blood Should be examined if it remains clearly elevated over 
 a longer period the dose should be reduced or withdrawn.

Whilst on treatment:
- Patients must be asked to promptly report muscle pain, cramps, or weakness especially if accompanied 
 by malaise or fever.
- If such symptoms occur whilst patients is receiving treatment with Atorvastatin, their CPK levels should 
 be measured. If these level are found to be significantly elevated (>5 times ULN), treatment should be  stopped.
- If muscular symptoms are severe and cause dialy discomfort, even if the CPK levels are elevated to ≤
 5 × ULN,treatment discontinuation should be considered.If symptoms resolve and CPK levels return 
 to normal, than re-introduction of Atorvastatin or introduction of an alternative statin may be 
 considered at the lowest dose and with close monitoring.
- Atorvastatin must be discontinued if cilincally significant elevation of CPK levels (> 10 × ULN ) 
 occur, or if rhabdomyolysis is diagnosed or suspected.  

 Atorva®plus film coated tablet  (Blister of 10 tablets, pack of 3 blisters.) 
 

 Store in a dry  place  at a temperature  below 25oC.