Clinical medicine profile
Diltiazem Gel
Calcium-channel blocker
- Route
- ORAL
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CONTRAINDICATIONS Diltiazem hydrochloride is contraindicated in (1) patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.
Precautions
- WARNINGS Cardiac Conduction : Diltiazem hydrochloride prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome.
- This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block (13 of 3290 patients or 0.40%).
- Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction.
- A patient with Prinzmetal's angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem (see ADVERSE REACTIONS ).
- Congestive Heart Failure : Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dP/dt).
- An acute study of oral diltiazem in patients with impaired ventricular function (ejection fraction 24% ± 6%) showed improvement in indices of ventricular function without significant decrease in contractile function (dP/dt).
- Worsening of congestive heart failure has been reported in patients with preexisting impairment of ventricular function.
- Experience with the use of diltiazem hydrochloride in combination with beta-blockers in patients with impaired ventricular function is limited.
- Caution should be exercised when using this combination.
- Hypotension : Decreases in blood pressure associated with diltiazem hydrochloride therapy may occasionally result in symptomatic hypotension.
- Acute Hepatic Injury : Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies.
- Such elevations were usually transient and frequently resolved even with continued diltiazem treatment.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION Patients controlled on diltiazem alone or in combination with other medications may be switched to diltiazem hydrochloride extended-release capsules, USP at the nearest equivalent total daily dose. Higher doses of diltiazem hydrochloride extended-release capsules, USP may be needed in some patients. Monitor patients closely. Subsequent titration to higher or lower doses may be necessary. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose. Hypertension : Adjust dosage to individual patient needs. When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, schedule dosage adjustments accordingly. The usual dosage range studied in clinical trials was 240 to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. Angina : Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period. Concomitant Use with Other Cardiovascular Agents Sublingual NTG : May be taken as required to abort acute anginal attacks during diltiazem hydrochloride therapy. P r ophylactic Nitrate Therapy : Diltiazem hydrochloride extended-release capsules, USP may be safely coadministered with short- and long-acting nitrates. Beta-blockers : (see WARNINGS and PRECAUTIONS ). Antihypertensives : Diltiazem hydrochloride extended-release capsules, USP have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release capsules, USP or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Generally no major renal dose change for amlodipine; monitor BP response.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic impairment increases exposure — start low.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Diltiazem hydrochloride extended-release capsules are indicated for the treatment of hypertension.
- It may be used alone or in combination with other antihypertensive medications.
- Diltiazem hydrochloride extended-release capsules are indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Adverse effects
- ADVERSE REACTIONS Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies.
- The following table presents the most common adverse reactions reported in placebo-controlled angina and hypertension trials in patients receiving diltiazem hydrochloride extended-release capsules up to 360 mg with rates in placebo patients shown for comparison.
- In addition, the following events were reported infrequently (less than 1%) in angina or hypertension trials: Cardiovascular: Congestive heart failure, palpitations, syncope, ventricular extrasystoles.
- Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor.
- G astrointestinal: Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, mild elevations of SGOT, SGPT, LDH, and alkaline phosphatase (see WARNINGS, Acute Hepatic Injury ), thirst, vomiting, weight increase.
- Dermatological: Petechiae, photosensitivity, pruritus, urticaria.
- Other: Amblyopia, CPK increase, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties.
- The following postmarketing events have been reported infrequently in patients receiving diltiazem hydrochloride: acute generalized exanthematous pustulosis, allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), purpura, retinopathy, myopathy, 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, some 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 REACTIONS, contact Ingenus Pharmaceuticals, LLC Toll-Free at 1-877-748-1970 or FDA at 1-800-FDA-1088 or w w w.fda.gov/medwatch .
Drug interactions
Open multi-drug checker ↗- First-line antihypertensive class in many Black African patients per guidelines.
- Oedema is dose-related
- may improve with ACEI/ARB combination rather than diuretic alone.
- Do not crush modified-release products unless licensed.
Mechanism & disposition
Dihydropyridine CCBs block L-type calcium channels in vascular smooth muscle, causing arterial vasodilation and reduced peripheral resistance.
Read complete mechanism
Dihydropyridine CCBs block L-type calcium channels in vascular smooth muscle, causing arterial vasodilation and reduced peripheral resistance. Non-dihydropyridines (verapamil/diltiazem) also depress cardiac conduction and contractility — useful for rate control.
Hours (chronic BP effect over days–weeks)
24 hours (most once-daily DHPs)
ORAL
occurs throughout the dosing interval. When diltiazem hydrochloride extended-release capsules were coadministered with a high fat content breakfast, the extent of diltiazem absorption was not affected. Dose-dumping does not occur. The apparent
Diltiazem is well absorbed from the gastrointestinal tract and is subject to an extensive first-pass effect, giving an absolute bioavailability (compared to intravenous administration) of about 40%. Diltiazem hydrochloride undergoes extensive metabolism in which only 2% to 4% of...
half-life following single or multiple drug administration is approximately 3.0 to 4.5 hours. Desacetyl diltiazem is also present in the plasma at levels of 10% to 20% of the parent drug and is 25% to 50% as potent as a coronary vasodilator as diltiazem. Minimum therapeutic plasm...
of total radioactivity is about 20 hours compared to 2 to 5 hours for diltiazem. In vitro binding studies show diltiazem hydrochloride is 70% to 80% bound to plasma proteins. Competitive in vitro ligand binding studies have also shown diltiazem hydrochloride binding is not altere...
Pregnancy, lactation & diet
Pregnancy Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from five to ten times greater (on a mg/kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities. In the perinatal/postnatal studies, there was an increased incidence of stillbirths at doses of 20 times the human dose or greater. There are no well-controlled studies in pregnant women; therefore, use diltiazem hydrochloride in pregnant women only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers Diltiazem is excreted in human milk. One report suggests that concentrations in breast milk may approximate serum levels. If use of diltiazem hydrochloride is deemed essential, an alternative method of infant feeding should be instituted.
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.