Aliskiren and hydrochlorothiazide

Name: Aliskiren and hydrochlorothiazide

Precautions While Using aliskiren and hydrochlorothiazide

It is very important that your doctor check your progress at regular visits to make sure aliskiren and hydrochlorothiazide is working properly. Blood tests may be needed to check for unwanted effects.

Using aliskiren and hydrochlorothiazide while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

aliskiren and hydrochlorothiazide may cause serious allergic reactions, including anaphylaxis and angioedema. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, lips, tongue, or throat while you are using aliskiren and hydrochlorothiazide.

You should not use aliskiren and hydrochlorothiazide (unless your doctor specifically tells you to) if you are also receiving cyclosporine (Gengraf®, Neoral®, Sandimmune®), itraconazole (Sporanox®), or lithium (Eskalith®, Lithobid®).

Dizziness, lightheadedness, or fainting may occur after the first dose, especially if you have been taking a diuretic (water pill). Make sure you know how you react to the medicine before you drive, use machines, or do other things that could be dangerous if you are dizzy or not alert. If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning. If you faint, stop using aliskiren and hydrochlorothiazide until you have talked to your doctor.

Check with your doctor if you become sick while taking aliskiren and hydrochlorothiazide, especially with severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water or salt and may lead to low blood pressure. You can also lose water by sweating, so drink plenty of water during exercise or in hot weather.

Hyperkalemia (high potassium in the blood) may occur while you are using aliskiren and hydrochlorothiazide. Check with your doctor right away if you have the following symptoms: abdominal or stomach pain, confusion, difficulty with breathing, irregular heartbeat, nausea or vomiting, nervousness, numbness or tingling in the hands, feet, or lips, shortness of breath, or weakness or heaviness of the legs. Ask your doctor before you use medicines, supplements, or salt substitutes that contain potassium.

Check with your doctor immediately if blurred vision, difficulty in reading, eye pain, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may increase your blood pressure.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Trouble swallowing.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • This medicine can cause certain eye problems. If left untreated, this can lead to lasting eyesight loss. If eye problems happen, signs like change in eyesight or eye pain most often happen within hours to weeks of starting aliskiren and hydrochlorothiazide. Call your doctor right away if you have these signs.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

How do I store and/or throw out Aliskiren and Hydrochlorothiazide?

  • Store in the original container at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Contraindications

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

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.

Documentation of allergenic cross-reactivity for thiazide-type diuretics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

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.

For Healthcare Professionals

Applies to aliskiren / hydrochlorothiazide: oral tablet

Hypersensitivity

Aliskiren:
Frequency not reported: Angioedema (face, hands, and body) with or without respiratory symptoms
Postmarketing reports: Angioedema

Hydrochlorothiazide:
Uncommon (0.1% to 1%): Rash
Rare (less than 0.1%): Anaphylaxis[Ref]

Two cases of angioedema with respiratory symptoms were reported with aliskiren use in clinical studies, and two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation. The rate of angioedema cases in completed studies was 0.06%. Twenty-six other cases of edema involving the face, hands, or whole body were reported with aliskiren use, including four which led to discontinuation. In the placebo controlled studies, the incidence of edema involving the face, hands or whole body was 0.4% with aliskiren compared with 0.5% with placebo.[Ref]

Metabolic

Frequency not reported: Edema, peripheral edema

Aliskiren:
Uncommon (0.1% to 1%): Elevated uric acid, gout, renal stones
Postmarketing reports: Peripheral edema, hyponatremia

Hydrochlorothiazide:
Very common (10% or more): Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients, and may predispose patients to cardiac arrhythmias
Common (1% to 10%): Metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, elevated serum uric acid levels
Very rare (less than 0.01%): Hot flushes
Frequency not reported: Edema, peripheral edema, glucose intolerance, a potentially deleterious effect on the lipid profile (i.e., increased serum cholesterol)[Ref]

Gastrointestinal

Aliskiren:
Common (1% to 10%): Diarrhea, abdominal pain, dyspepsia, gastroesophageal reflux (these side effects appear to be dose related)
Postmarketing reports: Nausea, vomiting

Hydrochlorothiazide:
Uncommon (0.1% to 1%): Nausea, vomiting, diarrhea[Ref]

In women and the elderly (65 years of age or older) receiving aliskiren therapy, increases in diarrhea rates were evident starting at a dose of 150 mg daily. Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation.[Ref]

Dermatologic

Aliskiren:
Common (1% to 10%): Rash
Rare (less than 0.1%): Angioedema (involving the face, hands, or whole body)
Postmarketing reports: Severe cutaneous adverse reactions (including Stevens Johnson syndrome and toxic epidermal necrolysis)

Hydrochlorothiazide:
Rare (less than 0.1%): Erythema annular centrifugum, acute eczematous dermatitis, morbilliform and leukocytoclastic vasculitis, phototoxic dermatitis
Frequency not reported: Subacute cutaneous lupus erythematosus like reaction[Ref]

Nervous system

Uncommon (0.1% to 1%): Malaise, pain
Frequency not reported: Fatigue

Aliskiren:
Frequency not reported: Headache, dizziness, fatigue, episodes of tonic-clonic seizures with loss of consciousness

Hydrochlorothiazide:
Frequency not reported: Cerebrovascular insufficiency associated with hydrochlorothiazide-induced plasma volume contraction, cognitive and neurologic impairment (i.e., confusion, somnolence, feeling dazed)- Symptoms resolved following discontinuation of hydrochlorothiazide.[Ref]

Episodes of tonic-clonic seizures were reported in two patients treated with aliskiren in the clinical trials. One patient had predisposing causes for seizures and a negative electroencephalogram (EEG) and cerebral imaging following the seizures (the other patient's EEG and imaging results were not reported). Aliskiren was discontinued and there was no rechallenge.[Ref]

Hepatic

Common (1% to 10%): Occasional elevations (greater than 150% from baseline) in ALT (SGPT)

Hydrochlorothiazide:
Rare (less than 0.1%): Interstitial nephritis[Ref]

Renal

Hydrochlorothiazide:
Rare (less than 0.1%): Renal insufficiency, renal failure, renal dysfunction, interstitial nephritis[Ref]

Hematologic

Hydrochlorothiazide:
Rare (less than 0.1%): Immune-complex hemolytic anemia, aplastic anemia, thrombocytopenia[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Asthenia, rigors

Hydrochlorothiazide:
Uncommon (0.1% to 1%): Myalgias, chills, muscle spasms, preservation of mineral bone density in older patients[Ref]

Ocular

Hydrochlorothiazide:
Frequency not reported: Transient blurred vision, acute transient myopia, acute angle-closure glaucoma, xanthopsia[Ref]

Respiratory

Aliskiren:
Frequency not reported: Nasopharyngitis, upper respiratory tract infection, cough

Hydrochlorothiazide:
Frequency not reported: Acute noncardiogenic pulmonary edema (these cases are thought to be due to idiosyncrasy or a hypersensitivity mechanism)[Ref]

Other

Rare (less than 0.1%): Parosmia
Frequency not reported: Tinnitus[Ref]

Immunologic

Hydrochlorothiazide:
Common (1% to 10%): Rash that is histologically identical to subacute cutaneous lupus
Frequency not reported: Allergic vasculitis, hemolytic anemia

Cardiovascular

Aliskiren:
Rare (less than 0.1%): Hypotension

Hydrochlorothiazide:
Frequency not reported: Cardiac arrhythmias (including ventricular ectopy and complete AV heart block), hypotension, orthostatic hypotension (more common in the elderly)[Ref]

Some side effects of aliskiren / hydrochlorothiazide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Liver Dose Adjustments

No adjustment recommended

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