a- Contraindications:

       • Active liver disease or unexplained persistent elevations of hepatic transaminase levels

       • Hypersensitivity to any component of Atrozemb®

       • Pregnancy and lactation

 

 

b- Warnings and precautions:

    • Myopathy/Rhabdomyolysis:

 

       - Atorvastatin:

            ◘ Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin

            ◘ Use of higher doses of atorvastatin with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole,

               and HIV protease inhibitors) increases the risk of myopathy/rhabdomyolysis

            ◘ Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK.

               caution should be exercised when prescribing Atrozemb® with colchicine

            ◘ Atrozemb® therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy

 

       - Ezetimibe:

            ◘ In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the

               relevant control arm (placebo or statin alone). However, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-

               lowering drugs

 

    • Liver Enzymes:

            It is recommended that liver enzyme tests be obtained prior to initiating therapy with Atrozemb® and repeated as clinically indicated.

            If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Atrozemb®, promptly interrupt

            therapy

           ○  Atrozemb® should be used with caution in patients who consume substantial quantities of alcohol

    • Endocrine Function:

            Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin

Side Effects

- Side effects:

      • Rhabdomyolysis and myopathy

      • Liver enzyme abnormalities

      • Myalgia

      • Abdominal pain

      • Increased hepatic enzymes

 

- The most commonly reported adverse reactions were:

      • increased ALT, increased AST, and musculoskeletal pain.

      • Other Adverse reactions:

      • Nervous system disorders: Dizziness

      • Respiratory, thoracic, and mediastinal disorders: Coughing

      • Gastrointestinal disorders: Abdominal pain, Nausea

      • Musculoskeletal and connective tissue disorders: Arthralgia, Muscle weakness, Musculoskeletal pain

      • Metabolism and nutrition disorders: Hyperkalemia

      • Infections and infestations: Bronchitis, Sinusitis

      • Vascular disorders: Hot flushes

      • Investigations: ALT increased, AST increased

 

- Other Adverse reactions were:

      • Nasopharyngitis

      • Arthralgia

      • Diarrhea

      • Pain in extremities

      • Urinary tract infections

      • Dyspepsia

      • Nausea

      • Musculoskeletal pain

      • Muscle spasms

      • Myalgia

      • Insomnia

      • Pharyngolaryngeal pain

      • Postmarketing Experience

 

- The additional events described below have been identified during post-approval use of ezetimibe and/or atorvastatin:

      • Blood and lymphatic system disorders: Thrombocytopenia

      • Nervous system disorders: Headache; Paresthesia; Peripheral neuropathy

      • There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion)

          associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon

          statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

      • Gastrointestinal disorders: Pancreatitis

      • Skin and subcutaneous tissue disorders: Angioedema; Bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic

          epidermal necrolysis); Rash; Urticarial

      • Musculoskeletal and connective tissue disorders: Myopathy/rhabdomyolysis

      • There have been rare reports of immune-mediated necrotizing myopathy associated with statin use

      • Injury, poisoning and procedural complications: Tendon rupture

      • Immune system disorders: Anaphylaxis; Hypersensitivity reactions

      • Hepatobiliary disorders: Hepatitis; Cholelithiasis; Cholecystitis; Fatal and nonfatal hepatic failure

      • Psychiatric disorders: Depression

      • Laboratory abnormalities: Elevated creatine phosphokinase

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