Olmesartan medoxomil and hydrochlorothiazide

Lithium: Risk of lithium toxicity ( 7.2 ) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic and antihypotensive effects; increased risk of renal toxicity ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.4 ) Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose ( 7.5 ) Antidiabetic drugs: Dosage adjustment may be required ( 7.6 ) Cholestyramine and colestipol: Reduced absorption of thiazides ( 7.6 )

7.1 Agents Increasing Serum Potassium Coadministration of BENICAR HCT with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Monitor serum lithium levels during concomitant use. 7.

3 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors Olmesartan medoxomil In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including olmesartan medoxomil) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving olmesartan medoxomil and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including olmesartan medoxomil may be attenuated by NSAIDs including selective COX-2 inhibitors. Hydrochlorothiazide In some patients the administration of a NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics. Therefore, monitor blood pressure closely.

7.4 Dual Blockade of the Renin Angiotensin System Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on BENICAR HCT and other agents that affect the RAS. Do not co-administer aliskiren with BENICAR HCT in patients with diabetes [see Contraindications (4) ].

Avoid use of aliskiren with BENICAR HCT in patients with renal impairment (GFR <60 ml/min).

7.5 Colesevelam H ydrochloride 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. Consider administering olmesartan at least 4 hours before the colesevelam hydrochloride dose [see Clinical Pharmacology (12.3) ] . 7. 6 The Use of Hydrochlorothiazide with Other Drugs When administered concurrently the following drugs may interact with thiazide diuretics: Antidiabetic drugs (oral agents and insulin) : Dosage adjustment of the antidiabetic drug may be required.

Ion exchange resins: Staggering the dosage of hydrochlorothiazide and ion exchange resins (e.g., cholestyramine, colestipol) such that hydrochlorothiazide is administered at least 4 hours before or 4 – 6 hours after the administration of resins would potentially minimize the interaction [see Clinical Pharmacology (12.3) ] . Corticosteroids, ACTH : Intensified electrolyte depletion, particularly hypokalemia.

8.1 Pregnancy Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity, and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue BENICAR HCT as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intraamniotic environment.

If oligohydramnios is observed, discontinue BENICAR HCT, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to BENICAR HCT for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4) ].

8.3 Nursing Mothers It is not known whether olmesartan is excreted in human milk, but olmesartan is secreted at low concentration in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue BENICAR HCT, taking into account the importance of the drug to the mother.