Azoren Drug Interactions

Potential interactions related to the Azoren combination: To be taken into account with concomitant use: Other antihypertensive agents: The blood pressure lowering effect of Azoren can be increased by concomitant use of other antihypertensive medicinal products (e.g. alpha blockers, diuretics).
Potential interactions related to the olmesartan medoxomil component of Azoren: Concomitant use not recommended: Medicinal products affecting potassium levels: Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e.g. heparin, ACE inhibitors) may lead to increases in serum potassium (see Precautions). If medicinal products which affect potassium levels are to be prescribed in combination with Azoren, monitoring of serum potassium levels is recommended.
Lithium: Reversible increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with ACE inhibitors and angiotensin II receptor antagonists, including olmesartan. Therefore, concomitant use of Azoren and lithium is not recommended (see Precautions). If concomitant use of Azoren and lithium proves necessary, careful monitoring of serum lithium levels is recommended.
Dual blockade of the RAAS: Clinical trial data has shown that dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events, such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see Contraindications and Precautions).
Concomitant use requiring caution: Use with aliskiren: Do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes (see Contraindications) because dual use is associated with increased risks of hypotension, hyperkalaemia, and changes in renal function (including acute renal failure) compared to monotherapy. Avoid use of aliskiren with olmesartan medoxomil in patients with renal impairment (GFR <60 mL/min).
Non-steroidal anti-inflammatory medicinal products (NSAIDs) including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day) and non-selective NSAIDs: When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of worsening of renal function and may lead to an increase in serum potassium. Therefore, monitoring of renal function at the beginning of such concomitant therapy is recommended, as well as adequate hydration of the patient.
Use with colesevelam hydrochloride: Concurrent administration of bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan. Administration of olmesartan at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect (see Pharmacology: Pharmacokinetics under Actions).
Additional information: After treatment with antacid (aluminium magnesium hydroxide), a modest reduction in bioavailability of olmesartan was observed.
Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin or the pharmacokinetics of digoxin. Co-administration of olmesartan medoxomil with pravastatin had no clinically relevant effects on the pharmacokinetics of either component in healthy subjects.
Olmesartan had no clinically relevant inhibitory effects on human cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1 and 3A4 in vitro, and had no or minimal inducing effects on rat cytochrome P450 activities. No clinically relevant interactions between olmesartan and medicinal products metabolised by the previously mentioned cytochrome P450 enzymes are expected.
Potential interactions related to the amlodipine component of Azoren: Effects of other medicinal products on amlodipine: CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus be required.
CYP3A4 inducers: There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers (i.e. rifampicin, Hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.
Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers, such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
Effects of amlodipine on other medicinal products: The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive agents.
In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine.
Simvastatin: Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
Tacrolimus: The co-administration of amlodipine with tacrolimus may increase exposure of tacrolimus. Because Azoren contains amlodipine, monitor tacrolimus blood levels during concomitant use.
Cyclosporine: In a prospective study in renal transplant patients, an average 40% increase in trough cyclosporine levels was observed in the presence of amlodipine. The co-administration of amlodipine with cyclosporine may increase exposure to cyclosporine. Because Azoren contains amlodipine, monitor trough cyclosporine levels during concomitant use.