Duowell Drug Interactions

Drug interaction studies with telmisartan 80 mg and rosuvastatin 20 mg in healthy volunteers showed that the Cmax of telmisartan in the presence of rosuvastatin increased about 1.35 fold and the AUC increased about 1.17 fold. The Cmax of rosuvastatin in the presence of telmisartan increased about twice and the AUC increased about 1.18 times. Studies of drug interactions with other medications and telmisartan/rosuvastatin combination agents have never been conducted, but individual studies on telmisartan and rosuvastatin have been performed as follows.
Telmisartan: The double blockade of the renin-angiotensin-aldosterone system (RAAS) by the combined administration of angiotensin II receptor antagonist (ARB), ACE inhibitor or aliskiren compared to single therapy of these drugs was related to increasing risk of hypotension, syncope, hyperkalemia and renal function changes (including acute renal failure). In patients who taken concomitant use of telmisartan and other medicines acting on RAAS, blood pressure, renal function and electrolyte should be closely monitored. Do not co-administer aliskiren with telmisartan in patients with diabetes or moderate to severe renal impairment (GFR <60 mL/min/1.73 m²).
It may increase the blood pressure lowering effect of other hypotensive medicines. No other clinically relevant interactions have been identified.
Coadministration of telmisartan did not result in a clinically significant interactions with warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, acetaminophen, simvastatin or amlodipine.
Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.
Ramipril: In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the AUC_0-24 and C_max of ramipril and ramiprilat. When combined with telmisartan and ramipril, the effect can be enhanced due to the pharmacodynamic effect and the increased exposure of the ramipril/ramiprilat. Concomitant use of ramipril and telmisartan is not recommended.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Telmisartan is not metabolized by the CYP-450 system and had no effects in vitro on CYP-450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit CYP-450 enzymes; it is also not expected to interact with drugs metabolized by CYP-450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.
Orthostatic hypotension may be aggravated by baclofen, amifostine, alcohol, barbiturates, drugs, and antidepressants.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs (i.e. acetylsalicylic acid (>3 g/day) at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.
Potassium sparing diuretics or potassium supplements: Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. Potassium sparing diuretics e.g. spironolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium. If concomitant use is indicated because of documented hypokalaemia they should be used with caution and with frequent monitoring of serum potassium.
Corticosteroids (systemic route): antihypertensive effect may be reduced when co-administered with this drug.
Diuretics (thiazides or loop diuretics): Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may result in volume depletion and in a risk of hypotension when initiating therapy with telmisartan.
Rosuvastatin: Effect of co-administered medicinal products on rosuvastatin: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of rosuvastatin with medicinal products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy. (See Table 6 as follows).

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Other medicinal products: Antacids: The simultaneous dosing of rosuvastatin with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%. This effect was mitigated when the antacid was dosed 2 hours after rosuvastatin. The clinical relevance of this interaction has not been studied.
Effect of rosuvastatin on co-administered medicinal products: Warfarin: Warfarin is not significantly affected by pharmacokinetics when used in combination with rosuvastatin. However, as with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of rosuvastatin in patients treated concomitantly with vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant) may result in an increase in International Normalised Ratio (INR). Discontinuation or down-titration of rosuvastatin may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.
Ciclosporin: Concomitant administration with rosuvastatin and ciclosporin did not affect plasma concentrations of ciclosporin.
Fenofibrate/Other fibrates: Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur.
Gemfibrozil, fenofibrate, other fibrates and lipid lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of a fibrate. These patients should also start with the 5 mg dose.
Oral contraceptives: Concomitant use of rosuvastatin and an oral contraceptive resulted in an increase in ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data available in subjects taking concomitant rosuvastatin and HRT and therefore a similar effect cannot be excluded. However, the combination has been extensively used in women in clinical trials and was well tolerated.
Effects on other drugs: Based on data from specific interaction studies no clinically relevant interaction with digoxin or ezetimibe is expected.