Clinical Studies Experience

The following serious adverse reactions are discussed in greater detail in other sections of the label:

• Risk of fetal/neonatal morbidity and mortality [See WARNINGS AND PRECAUTIONS].
• Head and neck angioedema [See WARNINGS AND PRECAUTIONS].
• Hypotension in volume- and/or salt-depleted patients [See WARNINGS AND PRECAUTIONS].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

Tekturna HCT

Tekturna HCT has been evaluated for safety in more than 2,700 patients, including over 700 treated for 6 months and 190 for over 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event (including uncontrolled hypertension) occurred in 2.7% of patients treated with Tekturna HCT versus 3.6% of patients given placebo.

Adverse events in placebo-controlled trials that occurred in at least 1% of patients treated with Tekturna HCT and at a higher incidence than placebo included dizziness (2.3% vs. 1%), influenza (2.3% vs. 1.6%), diarrhea (1.6% vs. 0.5%), cough (1.3% vs. 0.5%), vertigo (1.2% vs. 0.5%), asthenia (1.2% vs. 0%), and arthralgia (1% vs. 0.5%).

Aliskiren

Aliskiren has been evaluated for safety in 6,460 patients, including 1,740 treated for longer than 6 months, and 1,250 for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event, including uncontrolled hypertension occurred in 2.2% of patients treated with aliskiren, versus 3.5% of patients given placebo.

Two cases of angioedema with respiratory symptoms were reported with aliskiren use in the clinical studies. Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation. The rate of these angioedema cases in the completed studies was 0.06%.

In addition, 26 other cases of edema involving the face, hands, or whole body were reported with aliskiren use, including 4 leading to discontinuation.

In the placebo-controlled studies, however, the incidence of edema involving the face, hands, or whole body was 0.4% with aliskiren compared with 0.5% with placebo. In a long-term active-controlled study with aliskiren and HCTZ arms, the incidence of edema involving the face, hands, or whole body was 0.4% in both treatment arms.

Aliskiren produces dose-related gastrointestinal (GI) adverse reactions. Diarrhea was reported by 2.3% of patients at 300 mg, compared to 1.2% in placebo patients. In women and the elderly (age ≥ 65) increases in diarrhea rates were evident starting at a dose of 150 mg daily, with rates for these subgroups at 150 mg comparable to those seen at 300 mg for men or younger patients (all rates about 2% to 2.3%). Other GI symptoms included abdominal pain, dyspepsia, and gastroesophageal reflux, although increased rates for abdominal pain and dyspepsia were distinguished from placebo only at 600 mg daily. Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation.

Aliskiren was associated with a slight increase in cough in the placebo-controlled studies (1.1% for any aliskiren use vs. 0.6% for placebo). In active-controlled trials with ACE inhibitor (ramipril, lisinopril) arms, the rates of cough for the aliskiren arms were about one-third to one-half the rates in the ACE inhibitor arms.

Other adverse reactions with increased rates for aliskiren compared to placebo included rash (1% vs. 0.3%), elevated uric acid (0.4% vs. 0.1%), gout (0.2% vs. 0.1%), and renal stones (0.2% vs. 0%).

Single episodes of tonic-clonic seizures with loss of consciousness were reported in two patients treated with aliskiren in the clinical trials. One patient had predisposing causes for seizures and had a negative electroencephalogram (EEG) and cerebral imaging following the seizures; for the other patient, EEG and imaging results were not reported. Aliskiren was discontinued and there was no rechallenge in either case.

The following adverse events occurred in placebo-controlled clinical trials at an incidence of more than 1% of patients treated with aliskiren, but also occurred at about the same or greater incidence in patients receiving placebo: headache, nasopharyngitis, dizziness, fatigue, upper respiratory tract infection, back pain and cough.

No clinically meaningful changes in vital signs or in ECG (including QTc interval) were observed in patients treated with aliskiren.

Hydrochlorothiazide

Other adverse reactions that have been reported with hydrochlorothiazide, without regard to causality, are listed below:

Body As A Whole: weakness

Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation

Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;

Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions

Metabolic: hyperglycemia, glycosuria, hyperuricemia

Musculoskeletal: muscle spasm

Nervous System/Psychiatric: restlessness

Renal: renal failure, renal dysfunction, interstitial nephritis

Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis

Special Senses: transient blurred vision, xanthopsia

Clinical Laboratory Test Abnormalities

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Tekturna HCT.

Blood Urea Nitrogen (BUN)/Creatinine: Elevations (greater than 50% increase) in BUN and creatinine occurred in 11.8% and 0.9%, respectively, of patients taking Tekturna HCT, and 7% and 1.1%, respectively, of patients given placebo in short-term controlled clinical trials. No patients were discontinued due to an increase in either BUN or creatinine.

Hemoglobin and Hematocrit: A greater than 20% decrease in hemoglobin and hematocrit were observed in < 0.1% and 0.1%, respectively, of patients treated with Tekturna HCT, compared with 0% in placebo-treated patients. No patients were discontinued due to anemia.

Liver Function Tests: Occasional elevations (greater than 150%) in ALT (SGPT) were observed in 1.2% of patients treated with Tekturna HCT, compared with 0% in placebo-treated patients. No patients were discontinued due to abnormal liver function tests.

Serum Uric Acid: Uric acid related abnormalities were more commonly observed in patients treated with Tekturna HCT, compared with placebo; 2.2% versus 0% had a uric acid increase > 50% from baseline; gout and renal stones were less commonly observed.

Serum Electrolytes: [See WARNINGS AND PRECAUTIONS]

Post-Marketing Experience

The following adverse reactions have been reported in aliskiren post-marketing experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity: angioedema requiring airway management and hospitalization

Peripheral edema

Blood creatinine increased

Read the Tekturna HCT (aliskren and hydrochlorothiazide tablets) Side Effects Center for a complete guide to possible side effects »

No drug interaction studies have been conducted with Tekturna HCT and other drugs, although studies with the individual aliskiren and hydrochlorothiazide components are described below.

Aliskiren

Cyclosporine: Avoid co-administration of cyclosporine with aliskiren.

Itraconazole: Avoid co-administration of itraconazole with aliskiren. [See CLINICAL PHARMACOLOGY.]

Hydrochlorothiazide

When administered concurrently, the following drugs may interact with thiazide diuretics.

Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs: Additive effect or potentiation.

Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine): Possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxants.

Lithium: Should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity. Refer to the package insert for lithium before use of such preparation with Tekturna HCT.

Nonsteroidal anti-inflammatory drugs: In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Tekturna HCT and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Last reviewed on RxList: 11/1/2011
This monograph has been modified to include the generic and brand name in many instances.