Duowell Adverse Reactions

Telmisartan/rosuvastatin combination drug: According to clinical study of the combination therapy of rosuvastatin and telmisartan administered in 208 patients with hypertension and hyperlipidemia, the tolerability was good and no specific adverse reaction that occurred only in this group was reported, when compared to administration of single-dose telmisartan or rosuvastatin. In the group (82 patients) of combination therapy of rosuvastatin and telmisartan, adverse events related to this drug were as following; ALT increased, AST increased, CPK increased, dizziness and pruritus was reported each in 1 patient, and all adverse drug reactions were mild or moderate. All adverse events that occurred after administration were recorded as follows, even if they were not related to the test drug.
Digestive system: Dyspepsia, Paraesthesia oral.
Musculoskeletal and connective tissue disorders: Musculoskeletal stiffness.
Skin and subcutaneous tissue disorders: Acne, Pruritus.
Ear and labyrinth disorders: Vertigo.
Infections and infestations: Nasopharyngitis.
Investigations: Aspartate aminotransferase increased, Alanine aminotransferase increased, Blood creatine phosphokinase increased, Blood potassium increased, Glucose urine present.
Postmarket survey results in Korea: In Korea, 658 patients were surveyed for 6 years, and the incidence rate of adverse events was reported to be 21.12% (139/658 patients, 187 cases). The serious adverse drug reaction and unexpected adverse drug reactions were not reported.
In Korea, 1,503 patients were surveyed for 6 years, and the incidence rate of adverse events was reported to be 11.04% (166/1,503 patients, 292 cases). The serious adverse drug reaction was not reported, and unexpected adverse drug reactions were listed in the table as follows according to the frequency. (See Table 3.)

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The safety profile as follows is based on data from clinical trials and post-marketing experiences of the individual components, telmisartan and rosuvastatin.
Information linked to telmisartan: The overall incidence of adverse reactions reported with telmisartan was usually comparable to placebo (41.4% vs 43.9%) in placebo controlled trials in patients treated for hypertension. The incidence of adverse reactions was not dose related and showed no correlation with gender, age or race of the patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular morbidity was consistent with that obtained in hypertensive patients.
The adverse reactions listed as follows have been accumulated from controlled clinical trials in patients treated for hypertension and from post-marketing reports. The listing also takes into account serious adverse reactions and adverse reactions leading to discontinuation reported in three clinical long-term studies including 21,642 patients treated with telmisartan for the reduction of cardiovascular morbidity for up to six years.
Adverse reactions have been ranked under headings of frequency using the following convention: uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 4.)

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Metabolism disorders: cases of hypoglycemia have been rarely reported. (in diabetic patients) Patients should be monitored carefully. If the helplessness, hunger sensation, cold sweat, essential tremor, busy brain, convulsion, and decreased consciousness, it is recommended to stop the treatment and take proper action.
Angioedema: As swelling of the face, lips, tongue, or throat, the case of difficulty breathing or swallowing was reported. Patients should be monitored carefully. If the adverse events occurs, it is recommended to stop the treatment immediately and take proper action.
Hyperkalemia: Telmisartan may cause hyperkalemia. Use with caution in patients, and stop the treatment immediately and take proper action if the adverse events occurs.
Renal dysfunction: the case of renal failure were reported. Use with caution in patients, and stop the treatment immediately and take proper action if the adverse events occurs.
Shock, syncope, and loss of consciousness: Since syncope and loss of consciousness from hypotension, and shock may occur with telmisartan, use with caution in patients and take proper action if cold sensation, vomiting, and loss of consciousness occur. Specially, in patients with a hemodialysis, on low-salt diet, or taking diuretics, previously take low doses and titrate slowly with caution if necessary.
Dyshepatia, jaundice: Dyshepatia such as AST increased, ALT increased, ALP increased, LDH increased, and etc. and jaundice may occur with telmisartan. Use with caution in patients, and stop the treatment and take proper action if the adverse events occurs.
Anaphylaxis symptom: Allergic reactions including dyspnea, hypotension, or laryngeal edema may occur. Use with caution in patients, and stop the treatment immediately and take proper action if the adverse events occurs.
Interstitial lung disease (unknown frequency): Symptoms of interstitial lung disease like fever, cough, difficulty breathing, chest x-ray abnormalities may occur. In this case, stop the treatment and take proper action.
Rhabdomyolysis (unknown frequency): Rhabdomyolysis that the presenting features are myalgias, weakness, an elevated CK, and serum and urine myoglobin increased may occur. Use with caution in patients and take proper action like steroid therapy.
In addition to the previously mentioned adverse reactions, palpitation, fatigue and lack of effects were reported.
As the result of the large-scale post-marketing study on 15,601 hypertension patients in Korea, the overall incidence of adverse reactions was 1.54% (240 cases/15,601 cases), and the drug-related adverse reactions was 1.2% (183 cases/15,601 cases). The most common ADR was headache 0.38% (60 cases/15,601 cases) and followed dizziness 0.2% (33 cases/15,601 cases), coughing 0.13% (21 cases/15,601 cases), indigestion 0.07% (11 cases/15,601 cases), palpitation 0.06% (10 cases/15,601 cases). One case reported serious adverse reaction of arrhythmia. The following adverse reactions listed as follows, with no established causality, had lower incidence (*) than placebo in the pre-clinical trial or were the new adverse events that were not appeared in preclinical trials.
(Numbers in parentheses represent the number of cases.)
(1) Central and peripheral nervous system: headache*(60), facial spasm(2), paresthesia(2), paralysis(1).
(2) Respiratory system: coughing*(21), hyperpnea(1), pneumonia(1).
(3) Autonomic nerve: telangiectasia(5), erectile dysfunction(1), anorexia(1), arrhythmia(1).
(4) Whole body: impotent(4), edema(3).
(5) Psychiatric disorders: sexual desire disorder(2).
(6) Skin and subcutaneous tissue disorders: facial edema(1), rash(1), alopecia(1).
(7) Sensory system: conjunctivitis(1), tinnitus(1).
(8) Platelet hemorrhage and coagulation disorders: petechia(1).
Among these, the incidence of adverse reactions in patients with renal disease was 0.9% (4 cases/445 cases), and headache, dizziness, myalgia, and dermatitis were reported. The incidence of adverse reactions in patients with hepatopathy was 2.0% (6 cases/296 cases), and dizziness, indigestion, coughing, anorexia, impotent were reported.
Information linked to Rosuvastatin: The reported adverse events were generally mild and transient. In controlled clinical trials, less than 4% of rosuvastatin-treated patients were withdrawn due to adverse reactions.
The frequencies of adverse reactions are ranked according to the following convention: Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1000); Very rare (<1/10,000); Not known (cannot be estimated from the available data). (See Table 5.)

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As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent.
Renal effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with rosuvastatin. Shifts in urine protein from none or trace to ++ or more were seen in <1% of patients at some time during treatment with 10 and 20 mg, and in approximately 3% of patients treated with 40 mg. A minor increase in shift from none or trace to + was observed with the 20 mg dose. In most cases, proteinuria decreases or disappears spontaneously on continued therapy. Review of data from clinical trials and post-marketing experience to date has not identified a causal association between proteinuria and acute or progressive renal disease.
Skeletal muscle effects: Effects on skeletal muscle e.g. myalgia, myopathy (including myositis) and, rarely, rhabdomyolysis with and without acute renal failure have been reported in rosuvastatin-treated patients with all doses and in particular with doses >20 mg.
A dose-related increase in CK levels has been observed in patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient. If CK levels are elevated (>5xULN), treatment should be discontinued.
Liver effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in transaminases has been observed in a small number of patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient.
Experience after overseas marketing: In addition to the previously mentioned adverse events, the following adverse events were reported during postmarketing investigations.
Nervous system: Very rarely multiple neuropathy, amnesia.
Respiratory and thoracic: cough, dyspnea (frequency unknown).
Gastrointestinal: diarrhea (frequency unknown).
Hematologic disorder: thrombocytopenia (frequency unknown).
Hepatobiliary system: very rare jaundice, hepatitis, rarely increased transaminase.
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (frequency unknown).
Musculoskeletal: Very rarely arthritis, immune-mediated necrotizing myopathy (frequency unknown).
Renal: Very rarely hematuria.
Other: edema (frequency unknown).
The following adverse reactions have been reported with some statins.
Psychiatric: Depression, sleep disorders (including sleeping and nightmares) (frequency unknown).
Respiratory system: Exceptional cases such as interstitial lung disease especially during long term administration.
Reproductive system: Sexual dysfunction, gynecomastia (frequency unknown).
Hepatobiliary system: Fatal and nonfatal liver failure.
Post-marketing cognitive impairment with statin use is rarely reported. (eg. memory loss, forgetfulness, amnesia, memory impairment, confusion). These cognitive disorders have been reported in all statin drugs. These reports are generally inaccurate and reversible after discontinuation of medication, and there are deviations in symptom onset (1 day to several years) and symptom improvement (median 3 weeks).
Postmarket survey results in Korea: In Korea, 3,081 patients were surveyed for 6 years, and the incidence rate of harmful cases was 10.06% (310 cases, 415 cases). The most common ADR was headache 0.78% (24 persons, 24 cases) and followed dizziness 0.75% (23 patients, 23 cases), ALT increased 0.58% (18 patients, 18 cases), chest pain, cough and myalgia were reported in 0.49% (15 patients, 15 cases). And the drug-related adverse reactions was 2.92% (90 patients, 106 cases). The most common reported ADR was ALT increased 0.55% (17 patients, 17 cases) and followed myalgia 0.42% (13 patients, 13 cases), headache 0.39% (12 patients, 12 cases), CK increased 0.29% (9 patients, 9 cases), dizziness 0.26% (8 patients, 8 cases), constipation and AST increased 0.16% (5 patients, 5 cases) each, asthenia and joint pain 0.13% (4 patients, 4 cases) each, fatigue and anesthesia 0.10% (3 patients, 3 cases), sensory abnormality, chest discomfort, nausea, abdominal pain, diarrhea, anorexia, abdominal distension, itching and liver function test disorder 0.06% (2 patients, 2 cases) each, syncope, systemic pain, muscle spasms, gout, and erectile dysfunction 0.03% (1 patient, 1 case) each. One case of joint pain and myalgia was reported as a serious and unexpected drug adverse reaction. The unexpected adverse drug reactions that did not appear before the market were joint pain 0.13% (4 patients, 4 cases), fatigue and numbness were 0.10% (3 patients, 3 cases) each, sensory abnormality, chest discomfort, anorexia, abdominal distension and liver function test disorder 0.06% (2 patients, 2 cases) each, syncope, systemic pain, muscle spasm, gout, and erectile dysfunction were 0.03% (1 patients, 1 case) each. There were 98 adverse events reported voluntarily during the review period, of which two acute renal failure cases reported and single case of each oliguria, thrombocytopenia, and elevated serum creatinine were reported as serious and unexpected adverse drug reactions.