Filters
Custom request?
Type
Production region
Qualifications
Country of origin
Diltiazem API Manufacturers & Suppliers
12 verified results
All Diltiazem data. Full access. Full negotiation power
Commercial-scale Suppliers
Employees: 50+
All certificates
Employees: 10
All certificates
Employees: 19
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Diltiazem | CAS No: 42399-41-7 | GMP-certified suppliers
A medication that manages hypertension, improves exercise tolerance in stable and variant angina, and provides short-term intravenous control of rapid ventricular rate in arrhythmias.
Therapeutic categories
Primary indications
- Oral**
- Indicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents
- Indicated for use to improve exercise tolerance in patients with chronic stable angina
Product Snapshot
- Diltiazem is available as oral extended-release tablets, capsules, intravenous injections, and topical formulations, representing a small molecule cardiovascular agent with multiple administration routes
- It is primarily indicated for managing hypertension, stable and variant angina, atrial fibrillation/flutter rate control, and conversion of paroxysmal supraventricular tachycardias, with off-label topical and other systemic uses
- Diltiazem holds approved status in the United States and Canada, with regulatory acceptance for both oral and intravenous formulations
Clinical Overview
Pharmacologically, diltiazem exerts its effects by selectively inhibiting L-type calcium channels in both cardiac and vascular smooth muscle, thereby reducing calcium influx during membrane depolarization. Unlike dihydropyridine calcium channel blockers, diltiazem displays intermediate specificity influencing both myocardial contractility and vascular tone. This results in decreased heart rate (negative chronotropic effect), reduced myocardial contractility (negative inotropic effect), diminished AV nodal conduction, peripheral vasodilation, and lowered systemic vascular resistance. Collectively, these effects contribute to reduced myocardial oxygen demand and increased coronary blood flow, which improve exercise tolerance in angina patients.
Absorption of diltiazem is complete following oral administration, with extended-release and intravenous formulations available. The drug undergoes hepatic metabolism predominantly via cytochrome P450 enzymes (including CYP3A4) and demonstrates moderate plasma protein binding. Its elimination half-life allows once or twice daily dosing, with renal excretion accounting for minor clearance.
Safety considerations include the potential for bradycardia, hypotension, and conduction abnormalities. Caution is advised in patients with conduction system impairments or heart failure due to diltiazem’s negative inotropic and chronotropic properties. It is also associated with moderate risk of QT interval prolongation and can interact with multiple CYP450 substrates and inhibitors, warranting careful drug interaction assessment.
Diltiazem is marketed under various brand names worldwide, with Cardizem and Tiazac among the most commonly recognized. When sourcing the diltiazem API, quality considerations include verification of chemical purity, polymorphic form, and compliance with pharmacopoeial standards. Reliable suppliers should provide appropriate documentation demonstrating consistency in synthesis, absence of impurities, and stability, to ensure suitability for pharmaceutical formulation and regulatory submission.
Identification & chemistry
| Generic name | Diltiazem |
|---|---|
| Molecule type | Small molecule |
| CAS | 42399-41-7 |
| UNII | EE92BBP03H |
| DrugBank ID | DB00343 |
Pharmacology
| Summary | Diltiazem is a calcium channel blocker that inhibits voltage-dependent L-type calcium channels in cardiac and vascular smooth muscle, reducing intracellular calcium influx. This action decreases myocardial contractility and heart rate while promoting vasodilation, leading to lowered blood pressure and reduced myocardial oxygen demand. Therapeutically, diltiazem is utilized for managing hypertension, chronic stable angina, variant angina, and certain supraventricular tachyarrhythmias through modulation of cardiac conduction and vascular tone. |
|---|---|
| Mechanism of action | Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels associated with a high activation threshold and slow inactivation profile. L-type calcium channels are the main current responsible for the late phase of the pacemaker potential. Acting as the main Ca2+ source for contraction in smooth and cardiac muscle, activation of L-type calcium channels allows the influx of calcium ions into the muscles upon depolarization and excitation of the channel. It is proposed that this cation influx may also trigger the release of additional calcium ions from intracellular storage sites. Diltiazem is a slow calcium channel blocker that binds to the extracellular site of the alpha-1C subunit of the channel, which is thought to be the S5-6 linker region of the transmembrane domain IV and/or S6 segment of domain III. Diltiazem can get access to this binding site from either the intracellular or extracellular side, but it requires a voltage-induced conformational changes in the membrane. Diltiazem inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. In isolated human atrial and ventricular myocardium, diltiazem suppressed tension over the range of membrane potentials associated with calcium channel activity but had little effect on the tension-voltage relations at more positive potentials. This effect is thought to be mediated by the voltage-dependent block of the L-type calcium channels and inhibition of calcium ion release from the ER stores, without altering the sodium-calcium coupled transport or calcium sensitivity of myofilaments. Through inhibition of inward calcium current, diltiazem exerts a direct ionotropic and energy sparing effect on the myocardium. Diltiazem fslows atrioventricular nodal conduction, which is due to its ability to impede slow channel function. Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and therefore, decreased blood pressure. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. Through its actions on reducing calcium levels in cardiac and vascular smooth muscles, diltiazem causes a reduction in the contractile processes of the myocardial smooth muscle cells and vasodilation of the coronary and systemic arteries, including epicardial and subendocardial. This subsequently leads to increased oxygen delivery to the myocardial tissue, improved cardiac output due to increased stroke volume, decreased total peripheral resistance, decreased systemic blood pressure and heart rate, and decreased afterload. Diltiazem lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility; this leads to a therapeutic effect in improving exercise tolerance in chronic stable angina. |
| Pharmacodynamics | Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate). It is also considered a rate-control drug as it reduces heart rate. Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow. Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. In supraventricular tachycardia, diltiazem prolongs AV nodal refractories. As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension. In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo. In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed. When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Voltage-dependent L-type calcium channel subunit alpha-1C | Humans | blocker |
| Voltage-dependent calcium channel gamma-1 subunit | Humans | blocker |
ADME / PK
| Absorption | Diltiazem is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL. Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the peak plasma concentrations were reached between 11 and 18 hours post-dose. Diltiazem peak and systemic exposures were not affected by concurrent food intake. Due to hepatic first-pass metabolism, the absolute bioavailability following oral administration is about 40%, with the value ranging from 24 to 74% due to high interindividual variation in the first pass effect. The bioavailability may increase in patients with hepatic impairment. |
|---|---|
| Half-life | The plasma elimination half-life is approximately 3.0 to 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment. The apparent elimination half-life for diltiazem as extended-release tablets after single or multiple dosing is 6 to 9 hours. The plasma elimination half-life is approximately 3.4 hours following administration of a single intravenous injection. The elimination half-lives of pharmacologically active metabolites are longer than that of diltiazem. |
| Protein binding | Diltiazem is about 70-80% bound to plasma proteins, according to _in vitro_ binding studies. About 40% of the drug is thought to bind to alpha-1-glycoprotein at clinically significant concentrations while about 30% of the drug is bound to albumin. |
| Metabolism | Diltiazem is subject to extensive first-pass metabolism, which explains its relatively low absolute oral bioavailability. It undergoes N-demethylation primarily mediated by CYP3A4. CYP2D6 is responsible for O-demethylation and esterases mediate deacetylation. There was large inter-individual variability in the circulating plasma levels of metabolites in healthy volunteers. In healthy volunteers, the major circulating metabolites in the plasma are N-monodesmethyl diltilazem, deacetyl diltiazem, and deacetyl N-monodesmethyl diltiazem, which are all pharmacologically active. Deacetyl diltiazem retains about 25-50% of the pharmacological activity to that of the parent compound. Deacetyl diltiazem can be further transformed into deacetyl diltiazem N-oxide or deacetyl O-desmethyl diltiazem. N-monodesmethyl diltilazem can be further metabolized to N,O-didesmethyl diltiazem. Deacetyl N-monodesmethyl diltiazem can be further metabolized to deacetyl N,O-didesmethyl diltiazem, which can be glucuronidated or sulphated. Diltiazem can be O-demethylated by CYP2D6 to form O-desmethyl diltiazem. |
| Route of elimination | Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine. The major urinary metabolite in healthy volunnteers was N-monodesmethyl diltiazem, followed by deacetyl N,O-didesmethyl diltiazem, deacetyl N-monodesmethyl diltiazem, and deacetyl diltiazem; however, there seems to be large inter-individual variability in the urinary excretion of DTZ and its metabolites. |
| Volume of distribution | The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection in healthy male volunteers. |
| Clearance | Following a single intravenous injection in healthy male volunteers, the systemic clearance of diltiazem was approximately 65 L/h. After constant rate intravenous infusion, the systemic clearance decreased to 48 L/h. |
Formulation & handling
- Diltiazem is a small molecule available in multiple oral dosage forms including extended release tablets and capsules, as well as intravenous injectable formulations.
- Careful formulation considerations are required for oral extended release forms to ensure controlled drug release and maintain bioavailability.
- Avoid co-administration with natural licorice due to potential cardiovascular interactions; handle injectable powder under sterile conditions for reconstitution.
Regulatory status
| Lifecycle | The API has reached patent expiry in the United States as of 2011 and in Canada between 2012 and 2020, indicating market maturity and potential for generic competition in both regions. Products based on this API are available in the US and Canadian markets. |
|---|
| Markets | Canada, US |
|---|
Supply Chain
| Supply chain summary | Diltiazem is manufactured by multiple originator and generic pharmaceutical companies, indicating a competitive supply landscape. The product has branded presence primarily in the US and Canadian markets. Several patents have expired or are close to expiry between 2011 and 2021, supporting the existence of established generic competition. |
|---|
Safety
| Toxicity | **Clinical Toxicity and Overdose** The oral LD<sub>50</sub> ranges from 415 to 740mg/kg in mice and 560 to 810 mg/kg in rats. The oral LD<sub>50</sub> in dogs is considered to be in excess of 50 mg/kg. A dose of 360 mg/kg resulted in lethality in monkeys. The intravenous LD<sub>50</sub> is 60 mg/kg in mice and 38 mg/kg in rats. Cases of overdose from doses ranging from less than 1 g to 18 g have been reported with diltiazem, with several cases involving multiple drug ingestions resulting in death. Overdoses were associated with bradycardia, hypotension, heart block, and cardiac failure that may manifest as dizziness, lightheadedness, and fatigue. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician. Diltiazem overdose should be responded with appropriate supportive measures and gastrointestinal decontamination. Bradycardia and heart block can be treated with atropine at doses ranging from 0.60 to 1.0 mg. In the case of bradycardia, if there is no response to vagal blockage, cautious administration of isoproterenol should be considered. Cardiac pacing can also be used to treat fixed high-degree AV block. In the case of heart failure, blood pressure may be maintained with the use of fluids and vasopressors, as well as inotropic agents such as [isoproterenol], [dopamine], or [dobutamine]. Other appropriate measures include ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Diltiazem does not appear to be removed by peritoneal or hemodialysis. **Non-clinical toxicity** In a 24-month study in rats receiving oral doses of up to 100 mg/kg/day, there was no evidence of carcinogenicity. There was also no mutagenic response _in vitro_ or _in vivo_ in mammalian cell assays or _in vitro_ bacterial assays. No evidence of impaired fertility was observed in a study performed in male and female rats receiving oral doses of up to 100 mg/kg/day. **Pregnancy and Lactation** In reproduction studies in animals, administration of diltiazem at doses ranging from five to twenty times the daily recommended human therapeutic dose resulted in cases of the embryo and fetal lethality and skeletal abnormalities, and an increase in the risk of stillbirths. There have been no up-to-date controlled studies that investigated the use of diltiazem in pregnant women. The use of diltiazem in pregnant women should be undertaken only if the potential benefit justifies the risk to the fetus. Diltiazem is excreted in human milk, where one report suggests that the concentrations in breast milk may approximate serum levels; therefore, the decision should be made to either discontinue nursing or the use of the drug after careful consideration of the clinical necessity of diltiazem therapy in the nursing mother. **Use in special populations** As there is limited information on the variable effects of diltiazem in geriatric patients, the initial therapy of diltiazem should involve the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Currently, there are no specific dosing guidelines for patients with renal or hepatic impairment. |
|---|
- Diltiazem demonstrates variable acute toxicity across species with oral LD₅₀ values ranging from 415 to 810 mg/kg in rodents and intravenous LD₅₀ values as low as 38 mg/kg, indicating potential for severe systemic effects upon overdose
- Overdose may result in critical cardiovascular effects including bradycardia, hypotension, heart block, and cardiac failure
- Careful handling to avoid exposure and accidental ingestion is advised
Diltiazem is a type of Calcium Channel Blockers
Calcium channel blockers (CCBs) are a subcategory of pharmaceutical active pharmaceutical ingredients (APIs) widely used in the treatment of various cardiovascular conditions. CCBs work by blocking the influx of calcium ions into smooth muscle cells and cardiac muscle cells, leading to vasodilation and reduced cardiac contractility.
CCBs are commonly prescribed to manage hypertension (high blood pressure), angina (chest pain), and certain arrhythmias (irregular heart rhythms). They are also effective in treating Raynaud's disease and migraine headaches. These medications exert their therapeutic effects by selectively inhibiting L-type calcium channels in the heart and blood vessels.
By blocking calcium channels, CCBs help relax and widen blood vessels, reducing peripheral resistance and improving blood flow. This mechanism of action lowers blood pressure, relieves angina symptoms, and helps prevent certain types of abnormal heart rhythms.
Some well-known CCBs include amlodipine, nifedipine, diltiazem, and verapamil. These medications are available in various formulations, including immediate-release and extended-release tablets, as well as injectable solutions.
It's important to note that CCBs may cause certain side effects, such as dizziness, headache, flushing, and ankle swelling. They may also interact with other medications, so it's crucial to consult a healthcare professional before starting or changing any CCB therapy.
In summary, Calcium channel blockers are a subcategory of cardiovascular medications that inhibit calcium channels, resulting in vasodilation, decreased cardiac contractility, and overall therapeutic effects in conditions such as hypertension, angina, and arrhythmias. Proper medical supervision and individualized treatment plans are essential for optimizing the use of CCBs.
Diltiazem (Calcium Channel Blockers), classified under Antihypertensive agents
Antihypertensive agents are a crucial category of pharmaceutical active pharmaceutical ingredients (APIs) used to treat high blood pressure, also known as hypertension. These medications are designed to lower blood pressure and reduce the risk of associated cardiovascular complications.
Antihypertensive agents function by targeting various mechanisms involved in blood pressure regulation. Some common classes of antihypertensive agents include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and diuretics.
ACE inhibitors work by inhibiting the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that constricts blood vessels. ARBs, on the other hand, block the receptors to which angiotensin II binds, thereby preventing its vasoconstrictive effects.
Beta-blockers reduce blood pressure by blocking the effects of adrenaline and noradrenaline, which are responsible for increasing heart rate and constricting blood vessels. CCBs inhibit calcium from entering the smooth muscles of blood vessels, resulting in relaxation and vasodilation. Diuretics promote the elimination of excess fluid and sodium from the body, reducing blood volume and thereby lowering blood pressure.
Antihypertensive agents are typically prescribed based on the individual patient's condition and specific needs. They can be used alone or in combination to achieve optimal blood pressure control. It is important to note that antihypertensive agents should be taken regularly as prescribed by a healthcare professional and may require periodic monitoring to ensure their effectiveness and manage any potential side effects.
In summary, antihypertensive agents play a vital role in the management of hypertension by targeting various mechanisms involved in blood pressure regulation. These medications offer significant benefits in reducing the risk of cardiovascular complications associated with high blood pressure.
Diltiazem API manufacturers & distributors
Compare qualified Diltiazem API suppliers worldwide. We currently have 12 companies offering Diltiazem API, with manufacturing taking place in 5 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Cambrex | Producer | Italy | Unknown | CoA, USDMF | 104 products |
| Chemeca Drugs pvt Ltd | Producer | India | India | CoA | 3 products |
| Divis Labs. | Producer | India | India | CoA, FDA, GMP, ISO9001, Other, USDMF, WC | 47 products |
| Duchefa Farma B.V. | Distributor | Netherlands | Italy | CoA, GMP, ISO9001, MSDS, WC | 170 products |
| Fermion | Producer | Finland | Finland | Other, BSE/TSE, CoA, GDP, GMP, MSDS, USDMF | 29 products |
| Lusochimica | Producer | Italy | Italy | CoA, USDMF | 23 products |
| Piramal Healthcare | Producer | United Kingdom | India | CoA, GMP, WC | 31 products |
| Piramal Pharma Solutions | Producer | India | Unknown | CEP, CoA, FDA, GMP, JDMF, USDMF, WC | 44 products |
| SETV Global | Producer | India | India | CoA, FDA, GMP | 515 products |
| Spansules Pharmatech Pvt ... | Producer | India | India | CoA | 2 products |
| Synthelabo T.C. | Producer | France | France | CEP, CoA | 1 products |
| Tenatra Exports Private L... | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, MSDS | 263 products |
When sending a request, specify which Diltiazem API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Diltiazem API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
