Duowell Special Precautions

It should be administered carefully to the following patients: The elderly.
Patients with hyperkalemia or pre-disposing factors for high levels of potassium in the blood.
Patients with moderate and mild hepatic impairment. (Monitor carefully, and the posology should not exceed 40 mg once daily.)
As with other HMG-CoA reductase inhibitors, this medicine should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease. It is recommended that liver function tests be carried out prior to the initiation of treatment. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with this medicine.
Patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Patients with ischaemic cardiopathy, ischaemic cardiovascular disease or cerebrovascular accident. (Excessive reduction of blood pressure could result in a myocardial infarction or stroke.)
Patients with gastroduodenal diseases such as active gastric or duodenal ulcer.
Patients with severe hypotension and renal insufficiency (patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney).
Patients with severe renal insufficiency (serum creatinine ≥3.0 mm/dL).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): The combined use of ACE-inhibitors and angiotensin II receptor blockers or aliskiren is not recommended.
Effects on skeletal muscle as with other HMG-CoA reductase inhibitors. e.g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in rosuvastatin-treated patients. There have been very rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with statins, including rosuvastatin. IMNM is clinically characterized by proximal muscle weakness and elevated serum creatine kinase (CK), which persist despite discontinuation of statin treatment.
As with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include: Renal impairment; Hypothyroidism; Personal or family history of hereditary muscular disorders; Previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate; Alcohol abuse; Age >70 years; Situations where an increase in plasma levels may occur; Concomitant use of fibrates.
In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated at baseline (>5xULN) treatment should not be started.
Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. CK levels should be measured in these patients.
Therapy should be discontinued if CK levels are markedly elevated (>5xULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤5x ULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing rosuvastatin or an alternative HMG-CoA reductase inhibitor at the lowest dose with close monitoring.
Routine monitoring of CK levels in asymptomatic patients is not warranted.
Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline (>5xULN) a confirmatory test should be carried out within 5~7 days. If the repeat test confirms a baseline CK >5xULN, treatment should not be started.
This medicine should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis. (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
In clinical trials there was no evidence of increased skeletal muscle effects in the small number of patients dosed with rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, ciclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors. Therefore, the combination of this medicine and gemfibrozil is not recommended. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of such combinations. The 40 mg dose is contraindicated with concomitant use of a fibrate.
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of rosuvastatin, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
Pharmacokinetic studies show an approximate 2-fold elevation in median AUC and C_max in Asian subjects compared with Caucasians. Rosuvastatin dosage should be adjusted in Asian patients.
General precautions: As a result of drug interaction studies between 80 mg of telmisartan and 20 mg of rosuvastatin, the Cmax and AUC of telmisartan in the presence of rosuvastatin increased about 1.35 times and 1.17 times, respectively, and the Cmax of rosuvastatin in the presence of telmisartan increased about twice and the AUC of that increased about 1.18 times. Therefore, the potential risk of Cmax increase in rosuvastatin should be assessed and the patient should be monitored closely.
Rosuvastatin single-agent clinical trials shows that musculoskeletal toxicity (including myalgia, myopathy (including myositis), and rarely rhabdomyolysis, etc.) with or without acute renal failure in all dose-treated patients (especially greater than 20 milligrams). And CK levels were dose-dependently increased in patients receiving rosuvastatin. Use with caution in patients who are susceptible to rhabdomyolysis. CK levels should be measured before administration of this medicine.
The baseline value can be used as a reference to determine whether the CK level has increased during the administration of this medicine. CK is not measured after intense exercise or other potential factors that may cause CK elevation because of difficulty in CK numerical analysis. If the CK value is significantly increased by 5 times the upper limit of normal at baseline, it should be measured again after 5 to 7 days to confirm the results. Treatment should not be started with this medicine if the CK level has increased significantly 5 times the upper limit of normal at baseline, even after 5 to 7 days. Periodic monitoring of CK levels is recommended after administration of this medicine. Also, patients who start treatment with rosuvastatin or who increase rosuvastatin dose should be informed of the risk of myopathy. If there is muscle pain, tenderness, muscular weakness or muscle spasms that cannot be accurately explained during the administration of rosuvastatin, patients should be advised to consult a doctor immediately. In this case, the CK level should be measured and the drug should be discontinued if the CK level is significantly increased (>5 times the normal upper limit). And discontinuation may also be determined by considering whether the severity of muscular symptoms and daily discomfort are caused regardless of the CK level. The lowest does of rosuvastatin, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Re-administration of this drug is not recommended if a suspected genetic myopathy is suspected. Also, the levels of transaminase (AST, ALT) should be monitored prior to administration of this medicine and monitored periodically after administration of this medicine. Rosuvastatin should be prescribed with caution in patients with elevated levels of transaminase and should be discontinued if the value of AST, SGOT, ALT or SGPT increases above 3 times the upper limit of normal.
Telmisartan: Renal impairment and kidney transplantation: Periodic monitoring of serum potassium and creatinine levels is recommended when administering this drug to renal patients. There is no experience regarding the administration of telmisartan in patients with recent kidney transplantation. This medicine does not require dose adjustment in renal patients including those receiving hemodialysis, and is not removed by hemodialysis.
Intravascular hypovolemia: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of this medicine. If hypotension occurs, lay the patient flat and inject intravenous injection of saline solution if necessary.
Other conditions with stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure. Similar results are expected in patients taking this medicine.
Electrolyte imbalance/hyperkalemia: The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalaemia. In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or in patients with intercurrent events, hyperkalaemia may be fatal. Before considering the concomitant use of medicinal products that affect the renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are: Diabetes mellitus, renal impairment, age (>70 years).
Combination with one or more other medicinal products that affect the renin-angiotensin-aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus), and trimethoprim.
Intercurrent events, in particular dehydratation, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).
This product should be stopped for 24 hours prior to surgery.
In patients with gastrointestinal disorders such as active stomach or duodenal ulcer, gastrometastatic adverse events were more frequent when telmisartan was taken than placebo. Gastrointestinal bleeding was rarely reported in clinical trials and appeared initially in patients with gastrointestinal disease. Therefore, this medicine should be prescribed with caution in patients with gastrointestinal disorders.
There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system. When the medicine is administered to patients with either or both renal artery stenosis, the elevation of serum creatinine or serum uric acid nitrogen is predicted similar to ACE inhibitors. In addition, it is recommended to avoid use except for the case where the treatment is inevitable, because telmisartan administration may deteriorate renal function by a reduction in the kidney blood flow and glomerular filtration pressure.
Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of telmisartan is not recommended.
In patients with diabetes with additional risk for cardiovascular disease (eg, patients with diabetes and coronary artery disease), hypotensive agents such as angiotensin II receptor antagonists or ACE blockers may cause fatal myocardial infarction and unexpected cardiovascular disease, so that the risk of death may increase. Coronary artery disease may not be diagnosed because diabetic patients do not have symptoms of the disease, so proper diagnosis assessment (eg, exercise stress test) for coronary artery disease should be conducted priority in diabetic patients before administration.
Use in Children: Safety and effectiveness in pediatric patients have not been established Telmisartan pharmacokinetics have not been investigated in patients <18 years of age.
Use in the Elderly: No initial dosage adjustment is necessary for elderly patients. The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years.
Rosuvastatin: Interstitial lung disease: Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.
Post-marketing cases of fatal and nonfatal hepatic insufficiency were rarely reported in patients taking statin products including rosuvastatin. Treatment should be discontinued immediately if symptoms of serious liver injury and/or hyperbilirubinemia or jaundice occurs during the administration of this medicine. If no other pathogens are found, this medicine should not be re-administered.
Increased HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors including rosuvastatin.
Diabetes Mellitus: Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, BMI>30kg/m², raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines. In the JUPITER study, the reported overall frequency of diabetes mellitus was 2.8% in rosuvastatin and 2.3% in placebo, mostly in patients with fasting glucose 5.6 to 6.9 mmol/L.
Genetic polymorphisms: Individual polymorphisms of SLCO1B1 c.521CC and ABCG2 c.421AA are associated with a higher rosuvastatin exposure (AUC) compared to the SLCO1B1 c.521TT or ABCG2 c.421CC genotypes. This specific genotyping is not established in clinical practice, but for patients who are known to have these types of polymorphisms, a lower daily dose of rosuvastatin is recommended.
Severe cutaneous adverse reactions: Severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life-threatening or fatal, have been reported with rosuvastatin. At the time of prescription, patients should be advised of the signs and symptoms of severe skin reactions and be closely monitored. If signs and symptoms suggestive of this reaction appears, rosuvastatin should be discontinued immediately and an alternative treatment should be considered. If the patient has developed a serious reaction such as SJS or DRESS with the use of rosuvastatin, treatment with this drug must not be restarted in this patient at any time.
Genetic polymorphism: Pharmacogenomics: Disposition of rosuvastatin, involves OATP1B1 and other transporter proteins. Higher plasma concentrations of rosuvastatin have been reported in very small groups of patients (n=3 to 5) who have two reduced function alleles of the gene that encodes OATP1B1 (SLCO1B1 521T > C). The frequency of this genotype (i.e., SLCO1B1 521 C/C) is generally lower than 5% in most racial/ethnic groups. The impact of this polymorphism on efficacy and/or safety has not been clearly established.
Use in Children: Administration of this drug is not recommended because the safety and efficacy of this drug has not been established in children.
Use in the Elderly: Excessive hypotension is generally not desirable for the elderly (cerebral infarction may occur). When administered to the elderly, this medicine should be administered with caution while observing the patient's condition.
Effects on ability to drive and use machines: Studies to determine the effect of this medicine on the ability to drive and use machines have not been conducted. However, when driving vehicles or operating machinery it should be taken into account that dizziness or drowsiness may occasionally occur when undergoing antihypertensive therapy such as telmisartan.