Cozaar XQ: Hypotension: In patients who are intravascularly volume-depleted (eg, those treated with high-dose diuretics) or with severe aortic stenosis, symptomatic hypotension may occur. Intravascular volume depletion should be corrected prior to administration of Cozaar XQ, or a lower starting dose should be used (see Dosage & Administration). Because of the gradual onset of action, acute hypotension is unlikely.
Liver Function Impairment: Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a lower dose of losartan should be considered for patients with a history of hepatic impairment (see Pharmacology and Pharmacokinetics under Actions, and Dosage & Administration).
Because amlodipine is extensively metabolized by the liver and the plasma elimination t½ is 56 hrs in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
Losartan: Hypersensitivity: Angioedema (see Adverse Reactions).
Electrolyte/Fluid Imbalance: Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. In a clinical study conducted in type 2 diabetic patients with proteinuria, the incidence of hyperkalemia was higher in the group treated with losartan as compared to the placebo group; however, few patients discontinued therapy due to hyperkalemia (see Adverse Reactions and Laboratory Test Findings).
Renal Function Impairment: As a consequence of inhibiting the renin-angiotensin system (RAAS), changes in renal function including renal failure have been reported in susceptible individuals; these changes in renal function may be reversible upon discontinuation of therapy.
Other drugs that affect the RAAS may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects have been reported with losartan; these changes in renal function may be reversible upon discontinuation of therapy.
Amlodipine: Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Use in Patients with Heart Failure: In a long-term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure of nonischaemic etiology, amlodipine was associated with increased reports of pulmonary edema despite no significant difference in the incidence of worsening heart failure as compared to placebo.
Effects on the Ability to Drive or Operate Machinery: No studies of the effects of Cozaar XQ on the ability to drive and operate machines have been performed. However, certain side effects that have been reported with Cozaar XQ may affect some patients' ability to drive or operate machinery. Individual responses to Cozaar XQ may vary (see Adverse Reactions).
Use in pregnancy: When used in pregnancy during the 2nd and 3rd trimesters, drugs that act directly on the renin-angiotensin system (RAS) can cause injury and even death in the developing fetus. When pregnancy is detected, Cozaar XQ should be discontinued as soon as possible.
Although there is no experience with the use of Cozaar XQ in pregnant women, animal studies with losartan potassium have demonstrated fetal and neonatal injury and death, the mechanism of which is believed to be pharmacologically mediated through effects on the RAS. In humans, fetal renal perfusion, which is dependent upon the development of the RAS, begins in the 2nd trimester; thus, risk to the fetus increases if Cozaar XQ is administered during the 2nd or 3rd trimesters of pregnancy.
There are no adequate and well-controlled studies of amlodipine in pregnant women. The safety of amlodipine in pregnant women has not been established. Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at the dose 50 times the maximum recommended human dose.
Use in lactation: While it is not known whether losartan or amlodipine is excreted in human milk, significant levels of amlodipine and/or losartan active metabolite were shown to be present in animal milk. Therefore, nursing mothers should not receive Cozaar XQ.
Use in children: Since safety and efficacy of Cozaar XQ in patients ≤18 years has not been established, administration of Cozaar XQ is not recommended.
Use in the elderly: In clinical studies, there was no age-related difference in the efficacy or safety profile of losartan. Because of decreased clearance of amlodipine in the elderly, with a resulting increase of AUC of approximately 40-60% amlodipine therapy should usually be initiated at 2.5 mg daily. Since amlodipine 2.5 mg dose is not available with Cozaar XQ, this dose should be achieved with amlodipine monotherapy.