Medical Editor: John P. Cunha, DO, FACOEP
What Is Taztia XT?
Taztia XT (diltiazem hydrochloride capsule, extended release) is a calcium ion cellular influx inhibitor (slow channel blocker) indicated to treat high blood pressure (hypertension), used alone or in combination with other antihypertensive medications. Taztia XT is also indicated for the treatment of chronic stable angina.
What Are Side Effects of Taztia XT?
Side effects of Taztia XT include:
- swelling of extremities,
- widening of blood vessels, which can cause flushing or warmth (vasodilation),
- sore throat,
- nervousness, and
Dosage for Taztia XT
The usual starting doses of Taztia XT to treat hypertension are 120 to 240 mg once daily.
The initial dose of Taztia XT to treat angina is 120 mg to 180 mg once daily. Individual patients may respond to higher doses of up to 540 mg once daily.
Taztia XT In Children
Safety and effectiveness of Taztia XT in children have not been established.
What Drugs, Substances, or Supplements Interact with Taztia XT?
Taztia XT may interact with other medicines such as:
- rifampin, and
Tell your doctor all medications and supplements you use.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Serious adverse reactions have been rare in studies with diltiazem hydrochloride extended-release capsules (once-a-day dosage), as well as with other diltiazem formulations. It should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies. A total of 256 hypertensives were treated for between 4 and 8 weeks; a total of 207 patients with chronic stable angina were treated for 3 weeks with doses of diltiazem hydrochloride extended-release capsules (once-a-day dosage) ranging from 120 to 540 mg once daily. Two patients experienced first-degree AV block at the 540 mg dose. The following table presents the most common adverse reactions, whether or not drug-related, reported in placebo-controlled trials in patients receiving diltiazem hydrochloride extendedrelease capsules (once-a-day dosage) up to 360 mg and up to 540 mg with rates in placebo patients shown for comparison.
MOST COMMON ADVERSE EVENTS IN DOUBLE-BLIND PLACEBO-CONTROLLED HYPERTENSION TRIALS*
|Placebo||Diltiazem Hydrochloride Extended-Release Capsules
|n = 57
# pts (%)
|Up to 360 mg
n = 149
# pts (%)
n = 48
# pts (%)
|edema, peripheral||1 (2)||8 (5)||7 (15)|
|dizziness||4 (7)||6 (4)||2 (4)|
|vasodilation||1 (2)||5 (3)||1 (2)|
|dyspepsia||0 (0)||7 (5)||0 (0)|
|pharyngitis||2 (4)||3 (2)||3 (6)|
|rash||0 (0)||3 (2)||0 (0)|
|infection||2 (4)||2 (1)||1 (2)|
|diarrhea||0 (0)||2 (1)||1 (2)|
|palpitations||0 (0)||2 (1)||1 (2)|
|nervousness||0 (0)||3 (2)||0 (0)|
MOST COMMON ADVERSE EVENTS IN DOUBLE-BLIND PLACEBO-CONTROLLED ANGINA TRIALS*
|Placebo||Diltiazem Hydrochloride Extended-Release Capsules
|n = 50
# pts (%)
|Up to 360 mg
n = 158
# pts (%)
n = 49
# pts (%)
|headache||1 (2)||13 (8)||4 (8)|
|edema, peripheral||1 (2)||3 (2)||5 (10)|
|pain||1 (2)||10 (6)||3 (6)|
|dizziness||0 (0)||5 (3)||5 (10)|
|asthenia||0 (0)||1 (1)||2 (4)|
|dyspepsia||0 (0)||2 (1)||3 (6)|
|dyspnea||0 (0)||1 (1)||2 (4)|
|AV block||0 (0)||0 (0)||2 (4)|
|infection||0 (0)||2 (1)||1 (2)|
|flu syndrome||0 (0)||0 (0)||1 (2)|
|cough increase||0 (0)||2 (1)||1 (2)|
|extrasystoles||0 (0)||0 (0)||1 (2)|
|gout||0 (0)||2 (1)||1 (2)|
|myalgia||0 (0)||0 (0)||1 (2)|
|impotence||0 (0)||0 (0)||1 (2)|
|conjunctivitis||0 (0)||0 (0)||1 (2)|
|rash||0 (0)||2 (1)||1 (2)|
|abdominal enlargement||0 (0)||0 (0)||1 (2)|
|*Adverse events occurring in treated patients at 2% or more than placebo-treated patients.|
In addition, the following events have been reported infrequently (less than 2%) in clinical trials with other diltiazem products:
Angina, arrhythmia, AV block (second-or third-degree), bundle branch block, congestive heart failure, ECG abnormalities, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles.
Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor.
Anorexia, constipation, diarrhea, dry mouth, dysgeusia, mild elevations of SGOT, SGPT, LDH, and alkaline phosphatase (see WARNINGS, Acute Hepatic Injury), nausea, thirst, vomiting, weight increase.
Petechiae, photosensitivity, pruritus.
Albuminuria, allergic reaction, amblyopia, asthenia, CPK increase, crystalluria, dyspnea, edema, epistaxis, eye irritation, headache, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, neck rigidity, nocturia, osteoarticular pain, pain, polyuria, rhinitis, sexual difficulties, gynecomastia.
In addition, the following postmarketing events have been reported infrequently in patients receiving diltiazem hydrochloride: acute generalized exanthematous pustulosis, alopecia, erythema multiforme, exfoliative dermatitis, Stevens- Johnson syndrome, toxic epidermal necrolysis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), leukopenia, purpura, retinopathy, and thrombocytopenia. In addition, events such as myocardial infarction have been observed which are not readily distinguishable from the natural history of the disease in these patients. A number of well-documented cases of generalized rash, characterized as leukocytoclastic vasculitis, have been reported. However, a definitive cause and effect relationship between these events and diltiazem hydrochloride therapy is yet to be established.
To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-272-5525 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.
Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem hydrochloride concomitantly with other agents known to affect cardiac contractility and/or conduction (see WARNINGS). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem hydrochloride extended-release capsules (once-a-day dosage) (see WARNINGS). As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of the enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels.
The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium channel blockers should be titrated carefully.
Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the Cmax by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increased (1.5-to 2.5-fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g., prolonged sedation) of both midazolam and triazolam.
Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem hydrochloride and beta-blockers is usually well tolerated, but available data are not sufficient to predict the effects of concomitant treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities. Administration of diltiazem hydrochloride concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects and bioavailability of propranolol was increased approximately 50%. In vitro, propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted (see WARNINGS).
In nine healthy subjects, diltiazem significantly increased the mean buspirone AUC 5.5-fold and Cmax 4.1-fold compared to placebo. The T½ and Tmax of buspirone were not significantly affected by diltiazem. Enhanced effects and increased toxicity of buspirone may be possible during concomitant administration with diltiazem. Subsequent dose adjustments may be necessary during coadministration, and should be based on clinical assessment.
Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.
A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and AUC (53%) after a 1-week course of cimetidine 1200 mg/day and a single dose of diltiazem 60 mg. Ranitidine produced smaller, non-significant increases. The effect may be mediated by cimetidine’s known inhibition of hepatic cytochrome P450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted.
Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor heart rate in patients receiving concomitant diltiazem and clonidine.
A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine dose ranging from 15% to 48% was necessary to maintain cyclosporine trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued.
The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated.
Administration of diltiazem hydrochloride with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem hydrochloride therapy to avoid possible over- or under-digitalization (see WARNINGS).
Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and diltiazem.
Diltiazem significantly increases the AUC(0→∞) of quinidine by 51%, T½ by 36%, and decreases its CLoral by 33%. Monitoring for quinidine adverse effects may be warranted and the dose adjusted accordingly.
Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered.
Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 is increased with concomitant use of diltiazem. When possible, use a non-CYP3A4- metabolized statin with diltiazem. Otherwise, reduce the dose for both diltiazem and the statin and monitor for signs and symptoms of muscle toxicity.
In a healthy volunteer cross-over study (N=10), coadministration of a single 20 mg dose of simvastatin at the end of a 14-day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. Subjects with increased average steady-state exposures of diltiazem showed a greater increase in simvastatin exposure. If coadministration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to 240 mg.
In a ten-subject randomized, open-label, 4-way cross-over study, coadministration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and Cmax versus lovastatin alone. In the same study, there was no significant change in 20 mg single dose pravastatin AUC and Cmax during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.
Read the entire FDA prescribing information for Taztia XT (Diltiazem Hydrochloride Extended Release Tablets)
© Taztia XT Patient Information is supplied by Cerner Multum, Inc. and Taztia XT Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.