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Aliskiren and Hydrochlorothiazide


General


Pronunciation

(a lis KYE ren & hye droe klor oh THYE a zide)


Brand Names: U.S.

  • Tekturna HCT

Indications


Use: Labeled Indications

Hypertension: Treatment of hypertension, including use as initial therapy in patients likely to need multiple antihypertensives for adequate control


Contraindications


US labeling: Hypersensitivity to aliskiren, hydrochlorothiazide, sulfonamide-derived drugs, or any component of the formulation; anuria; concomitant use with an ACE inhibitor or ARB in patients with diabetes mellitus

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See "Warnings/Precautions " � for more detail.

Canadian labeling: Additional contraindications (not in US labeling): History of angioedema with aliskiren, ACE inhibitors, or ARBs; hereditary or idiopathic angioedema; severe progressive renal disease (GFR <30 mL/minute/1.73 m2) and if increasing azotemia and oliguria occur during therapy; use in pregnant or breast-feeding women; hyponatremia, hypercalcemia, symptomatic hyperuricemia, and conditions involving enhanced potassium loss (refractory hypokalemia); concomitant use with ACE-inhibitors or ARBs in patients with GFR <60 mL/minute/1.73 m2; hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption; patients <2 years of age.


ALERT: U.S. Boxed Warning

Fetal toxicity:

When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Dosing and Administration


Dosing: Adult

Note: Dosage must be individualized. Combination product may be substituted for individual components in patients currently maintained on both agents separately or in patients not adequately controlled with monotherapy (using one of the agents or an agent within same antihypertensive class). The combination product is approved for use as initial therapy in the US labeling but is not approved for this indication in the Canadian labeling.

Hypertension: Oral:

Initial therapy: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg once daily, dose may be titrated at 2- to 4-week intervals; maximum recommended daily doses: Aliskiren 300 mg; hydrochlorothiazide 25 mg

Add-on therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect; maximum recommended daily doses: Aliskiren 300 mg; hydrochlorothiazide 25 mg

Replacement therapy: Substitute for the individually titrated components

Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment initiation.


Dosing: Geriatric

Refer to adult dosing. No initial dosage adjustment required.


Dosing: Renal Impairment

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); however, no adjustment necessary for aliskiren (Vaidyanathan 2007). Risk of hyperkalemia and progressive renal dysfunction may occur with aliskiren (use with caution). Hydrochlorothiazide is usually ineffective when CrCl <30 mL/minute and is contraindicated in patients who are anuric. The Canadian labeling contraindicates use of aliskiren/hydrochlorothiazide if GFR <30 mL/minute/1.73 m2.

ESRD (requiring hemodialysis): There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); however, no dosage adjustment necessary for aliskiren (Khadzhynov 2012). Risk of hyperkalemia is increased with chronic aliskiren therapy; use with extreme caution. Hydrochlorothiazide is usually ineffective when CrCl <30 mL/minute and is contraindicated in patients who are anuric.


Dosing: Hepatic Impairment

US labeling: Mild to severe impairment: No dosage adjustment necessary. Use with caution. See also Aliskiren and Hydrochlorothiazide individual monographs.

Canadian labeling:

Mild to moderate impairment: No dosage adjustment necessary. Use with caution.

Severe impairment: Use is not recommended.


Administration

Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended.


Dietary Considerations

May be taken with or without food; however, a high-fat meal reduces absorption. Consistent administration with regards to meals is recommended.


Storage

Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F). Protect from moisture.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tekturna HCT:

150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg

150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg

300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg

300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg


Drug Interactions

ACE Inhibitors: Aliskiren may enhance the hyperkalemic effect of ACE Inhibitors. Aliskiren may enhance the hypotensive effect of ACE Inhibitors. Aliskiren may enhance the nephrotoxic effect of ACE Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Angiotensin II Receptor Blockers: Aliskiren may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification

Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

AtorvaSTATin: May increase the serum concentration of Aliskiren. Monitor therapy

Barbiturates: May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Salts: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Aliskiren. Canagliflozin may enhance the hypotensive effect of Aliskiren. Monitor therapy

CarBAMazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Cyclophosphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced. Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of Aliskiren. Avoid combination

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Avoid combination

Drospirenone: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Monitor therapy

Grapefruit Juice: May decrease the serum concentration of Aliskiren. Management: Avoid concomitant use of aliskiren and grapefruit juice. Separation of aliskiren and grapefruit juice administration by several hours may reduce the chance for interaction. Monitor for decreased aliskiren levels/effects. Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Itraconazole: May increase the serum concentration of Aliskiren. Avoid combination

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Aliskiren. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Consider therapy modification

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

OXcarbazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Consider therapy modification

Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Monitor therapy

Verapamil: May increase the serum concentration of Aliskiren. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy


Monitoring Parameters

Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status


Lab Test Interferences


Test Interactions

See individual agents.


Adverse Reactions


Angioedema, periorbital edema, and peripheral edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.

Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.

>10%: Renal: Increased blood urea nitrogen (12%)

1% to 10%:

Central nervous system: Dizziness (2%), vertigo (1%)

Endocrine & metabolic: Hypokalemia (2%), increased uric acid (2%), hyperkalemia (1%)

Gastrointestinal: Diarrhea (2%)

Hepatic: Increased serum ALT (1%)

Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)

Respiratory: Flu-like symptoms (2%), cough (1%)

<1% (Limited to important or life-threatening): Decreased hematocrit, decreased hemoglobin


Warnings/Precautions


Concerns related to adverse effects:

- Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, or concomitant use with ACE inhibitors, ARBs, NSAIDs (including COX-2 inhibitors), potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia.

- Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz, 1997).

- Hypersensitivity: Anaphylaxis and angioedema have been reported. Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use with caution in any patient with a history of angioedema (of any etiology) as angioedema, some cases necessitating hospitalization and intubation, has been observed (rarely) with aliskiren use. Discontinue immediately following the occurrence of anaphylaxis or angioedema; do not readminister. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Early, aggressive, and appropriate management is critical. Hypersensitivity reactions may also occur with hydrochlorothiazide; risk is increased in patients with a history of allergy or bronchial asthma.

- Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients or with concomitant use of other agents acting on the renin-angiotensin-aldosterone system. Prior to initiation, correct hypovolemia or salt depletion, or closely monitor volume status in patients during treatment initiation. If hypotension does occur, this is not a contraindication for further use; once blood pressure has been stabilized, aliskiren usually can be continued without difficulty.

- Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

- Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur.

- Sulfonamide ( "sulfa " �) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett, 2004; Johnson, 2005; Slatore, 2004; Tornero, 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

- Diabetes mellitus: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Use of aliskiren (monotherapy or combined with ACE inhibitors or ARBs) in patients with type 2 diabetes mellitus has demonstrated an increased incidence of renal impairment, hypotension, and hyperkalemia; use is contraindicated in patients with diabetes mellitus who are taking an ACE inhibitor or ARB.

- Hepatic impairment: Use caution in patients with hepatic impairment. Titrate slowly. In progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma.

- Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia. The Canadian labeling contraindicates use in patients with hypercalcemia.

- Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides.

- Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion prior to initiating therapy.

- Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

- Renal impairment: Use with caution or avoid in patients with deteriorating renal function or low renal blood flow (eg, renal artery stenosis, severe heart failure, post-MI, volume depletion); may increase risk of developing acute renal failure and hyperkalemia. Thiazide diuretics are not recommended in patients with CrCl <30 mL/minute, loop diuretics are preferred over thiazides. Cumulative effects may develop, including azotemia, in patients with impaired renal function. Concomitant use of aliskiren with an ACE inhibitor, ARB, or NSAID (including COX-2 inhibitors) may increase risk of developing acute renal failure; concomitant use with an ACE inhibitor or ARB should be avoided in patients with GFR <60 mL/minute.

- Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Concurrent drug therapy:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.


Pregnancy Risk Factor

D


Pregnancy Considerations

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. See individual agents.


Actions


Pharmacology

Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience dizziness, loss of strength and energy, cough, diarrhea, or flu-like symptoms. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness or passing out, tachycardia, increased thirst, seizures, loss of strength and energy, lack of appetite, urinary retention or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting), difficulty swallowing, shortness of breath, excessive weight gain, swelling of arm or leg, vision changes, eye pain, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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