Diltiazem is a medication primarily used to treat high blood pressure (hypertension), angina (chest pain), and certain heart rhythm disorders. It belongs to a class of drugs called calcium channel blockers. These medications work by relaxing blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload.
Diltiazem (Cardizem) is a rate-limiting calcium-channel blocker, like verapamil, that is used in the treatment of patients with angina, hypertension, and cardiac arrhythmias.
Diltiazem (Cardizem) Uses:
- Oral:
- It can be used in the management of hypertension, chronic stable angina, vasospastic angina.
- Injection:
- It is administered parenterally to treat atrial fibrillation or atrial flutter, reduce acute ventricular rate, and convert supraventricular tachycardia.
- Off Label Use of Diltiazem in Adults:
- For topical use in anal fissures.
- Atrial fibrillation or atrial flutter
- chronic ventricular rate control
- Chest pain
- Hypertrophic cardiomyopathy.
- Idiopathic ventricular tachycardia.
- Non-sustained ventricular tachycardia or symptomatic ventricular premature beat.
- Pulmonary arterial hypertension (group 1).
- Raynaud phenomenon.
- When treating supraventricular tachycardia, such as atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia, and multifocal atrial tachycardia,
Diltiazem Dose in Adults:
Notes:
- Diltiazem is a medicine that helps treat high blood pressure, chest pain (angina), and certain heart rhythm problems.
- It's part of a group of drugs called calcium channel blockers.
Safety:
- Avoid using it with beta-blockers or in people with heart failure unless they have a pacemaker.
- Don't use it if someone has problems with their heart's natural pacemaker or has certain types of heart block without a pacemaker.
Forms:
- It comes in different types, like immediate-release tablets (usually taken four times a day), 12-hour extended-release capsules (taken twice a day), and 24-hour extended-release capsules (taken once a day). There's also an IV (intravenous) form for injections.
Dosage:
- The dose depends on the type of diltiazem and the condition being treated.
- Switching between different forms requires careful conversion, so it's important to follow a doctor's instructions closely.
Diltiazem (Cardizem) Dose in the treatment of Angina pectoris:
For chronic stable angina as an alternative treatment, diltiazem can be used in different forms and doses:
- Immediate-release tablets: Start with 30 mg, taken four times a day. Increase the dose as needed every 1 to 2 days until you reach the effective dose, usually between 240 to 360 mg per day in 3 to 4 doses.
- 12-hour (twice-daily) extended-release capsules (off-label): Begin with 60 mg twice daily. Increase the dose, if necessary, every 7 to 14 days until you reach the effective dose, typically between 240 to 360 mg per day in 2 doses.
- 24-hour (once-daily) extended-release capsules: Start with 120 to 180 mg once daily. Increase the dose as needed every 7 to 14 days until you reach the effective dose, usually between 240 to 360 mg per day.
For vasospastic angina, similar dosing applies:
- Immediate-release tablets: Start with 30 mg, taken four times a day. Increase the dose as needed every 1 to 2 days until you reach the effective dose, typically between 240 to 360 mg per day in 3 to 4 doses.
- 12-hour (twice-daily) extended-release capsules (off-label): Begin with 60 mg twice daily. Increase the dose, if necessary, every 7 to 14 days until you reach the effective dose, typically between 240 to 360 mg per day in 2 doses.
- 24-hour (once-daily) extended-release capsules: Start with 120 to 180 mg once daily. Increase the dose as needed every 7 to 14 days until you reach the effective dose, usually between 240 to 360 mg per day.
Diltiazem (Cardizem) Dose in the treatment of Chest pain associated with cocaine ingestion, with or without evidence of acute coronary syndrome (off-label):
- Initial bolus: Give 0.25 mg per kilogram of body weight over 2 minutes (average dose: 20 mg). This can be repeated after 15 minutes if necessary.
- Continuous infusion: Patients who respond well to 1 or 2 bolus doses can then be started on a continuous infusion if they continue to have symptoms despite receiving optimal therapy with nitro-glycerine.
It's important to note that this use of diltiazem is off-label, meaning it's not FDA-approved for this specific indication, but it may be used based on clinical judgment and evidence.
Diltiazem (Cardizem) Dose in the treatment of Atrial fibrillation or atrial flutter, rate control:
Acute ventricular rate control using intravenous (IV) administration:
- Bolus dose: Give 0.25 mg per kilogram of body weight over 2 minutes (average dose: 20 mg). If rate control is insufficient after 15 minutes, a repeat bolus dose of 0.35 mg per kilogram over 2 minutes may be given (average dose: 25 mg).
- Continuous infusion following bolus(es): Start with an initial infusion rate of 5 to 10 mg per hour. The infusion rate can be increased in 5 mg per hour increments according to the ventricular response, up to a maximum of 15 mg per hour. Avoid continuous infusion for more than 24 hours or exceeding 15 mg per hour due to the risk of drug accumulation.
Chronic ventricular rate control using oral administration (off-label):
- Immediate-release tablets: Start with 30 mg taken four times daily. Increase the dose as needed to achieve ventricular rate control, usually ranging from 120 to 480 mg per day in 3 or 4 divided doses.
- Extended-release capsules: Begin with 120 mg once daily or in 2 divided doses, depending on the formulation. Increase the dose as needed to achieve ventricular rate control, typically ranging from 120 to 480 mg per day.
Diltiazem (Cardizem) Dose as an alternative agent in the treatment of Hypertension:
Diltiazem can be used orally in different formulations and doses:
- 12-hour (twice-daily) formulations: Begin with 60 to 120 mg taken twice daily. Increase the dose as needed after approximately 7 to 14 days. The usual dose ranges from 240 to 360 mg per day, divided into 2 doses.
- 24-hour (once-daily) formulations: Start with 120 to 240 mg once daily. Increase the dose as needed after about 7 to 14 days. The usual dose ranges from 120 to 360 mg once daily.
Diltiazem (Cardizem) Dose as an alternative agent in the treatment of non-sustained ventricular tachycardia or ventricular premature beats, symptomatic (off-label):
- Initial dose: Start with 120 to 180 mg once daily or in divided doses depending on the formulation of the drug.
- Usual effective dose: Typically ranges from 240 to 360 mg per day.
Diltiazem (Cardizem Dose as an alternative agent in the treatment of Pulmonary arterial hypertension (group-1) (off-label):
- Oral formulation: Use 24-hour (once-daily) formulations.
- Initial dose: Start with 120 mg once daily.
- Titration: Increase the dose gradually and with close hemodynamic monitoring.
- Reported daily dose range: Typically ranges from 240 to 720 mg per day.
It's crucial to emphasize that diltiazem for pulmonary arterial hypertension should only be used in carefully selected patients who have undergone a positive vasoreactivity test and are under the close supervision of a pulmonary hypertension specialist. Regular monitoring and adjustment of the dosage are necessary to ensure optimal treatment outcomes.
Diltiazem (Cardizem) Dose as an alternative agent in the treatment of Supraventricular tachycardia:
Acute treatment (IV administration):
- Bolus dose: Give 0.25 mg per kilogram of actual body weight over 2 minutes (average dose: 20 mg). If the response is insufficient after at least 15 minutes, a repeat bolus dose of 0.35 mg per kilogram over 2 minutes may be given (average dose: 25 mg). If bolus(es) do not terminate the arrhythmia, consider alternative therapy.
Chronic maintenance (off-label use, oral administration):
- Immediate-release tablets: Start with 30 mg taken four times daily. Increase the dose as needed for heart rate control, up to a usual effective dose of 360 mg per day in divided doses.
- Extended-release capsules: Begin with 120 mg once daily or in 2 divided doses depending on the formulation. Increase the dose as needed for heart rate control, up to a usual effective dose of 360 mg per day.
Conversion between dosage forms:
- Immediate-release to extended-release formulations: Patients stabilized on a maintenance regimen between 120 and 360 mg of immediate-release tablets may be switched to an extended-release formulation at the same daily dose administered in 1 or 2 divided doses depending on the formulation. Dosage adjustment of the extended-release formulation may be necessary following conversion.
- IV infusion to oral: Start immediate-release oral medication about 1 hour before stopping the IV infusion. The oral daily dose may be estimated from the IV infusion rate using the provided equation. Round oral doses to the nearest appropriate strength and formulation.
Diltiazem (Cardizem) Dose in Children
Diltiazem (Cardizem) Dose in the treatment of Atrial tachyarrhythmias, rate control (bridge to therapy):
For infants ≥6 months, children, and adolescents:
- Initial bolus: Give 0.25 mg per kilogram over 5 minutes, with a maximum dose of 20 mg per dose (average adult dose).
- Continuous IV infusion: Following the bolus, start a continuous IV infusion. Reported rate range in one study was 0.05 to 0.15 mg per kilogram per hour. The dose should be individualized based on patient response.
- Dosage based on study: A small study of 10 patients with atrial tachycardia (aged 6 months to 21 years) found that an initial bolus of 0.25 mg/kg followed by a continuous infusion titrated to effect was effective. The reported effective range for infusion was 0.05 to 0.15 mg/kg/hour, with a mean infusion rate of 0.11 mg/kg/hour. Rate control was achieved in 9 of the 10 patients within 10 minutes of dosing. One patient required an additional bolus of 0.25 mg/kg.
- Duration of infusion: In the trial of 10 pediatric patients, the median duration was 45 hours (mean: 54 hours; range: 14 to 126 hours).
It's important to note that infusions exceeding 24 hours are not recommended in adults. If administration of diltiazem infusion exceeds 24 hours, potential effects such as decreased clearance, prolonged elimination half-life, and increased plasma concentrations should be considered.
Diltiazem (Cardizem) Dose in the treatment of Hypertension:
Infants and Children:
- Oral Immediate-release Formulations:
- Initial Dose: Start with 1.5 to 2 mg per kilogram per day, divided into 3 to 4 doses.
- Titration: Increase gradually at 1- to 2-day intervals until the optimum response is achieved.
- Maximum Daily Dose: The usual maximum daily dose is 3.5 mg per kilogram per day. Some experts recommend a higher maximum daily dose of up to 6 mg per kilogram per day, not exceeding 360 mg per day or the maximum tolerated dose, whichever is less.
- Note: Once the patient is stabilized on a total daily dose, they may be switched to an extended-release dosage form at the appropriate interval (once or twice daily) if they can swallow capsules whole and are receiving an adequate milligram amount.
Adolescents:
- Oral Immediate-release Formulations:
- Dose: 30 to 120 mg per dose, administered 3 to 4 times daily.
- Usual Daily Dosage Range: 180 to 360 mg per day.
- Oral Extended-release Formulations:
- Capsule, Extended Release (Once Daily Dosing; e.g., Cardizem CD, Tiazac): 120 to 300 mg once daily.
- Capsule, Extended Release (Twice Daily Dosing; e.g., Cardizem SR): 120 to 300 mg per day, divided into 2 doses.
Pregnancy Risk Factor C
- Diltiazem falls under Pregnancy Risk Factor C, meaning adverse events have been seen in animal studies.
- If hypertension treatment is necessary during pregnancy, other medications are usually preferred to avoid potential risks to the fetus, infant, and mother.
- However, women with hypertrophic cardiomyopathy who were already on diltiazem before pregnancy may continue treatment, although it's advised to have more frequent fetal monitoring to ensure the baby's well-being.
Diltiazem use during breastfeeding:
- Diltiazem can be found in breast milk in concentrations similar to those in the mother's blood.
- However, the manufacturer doesn't recommend breastfeeding while taking diltiazem due to potential risks.
Diltiazem (Cardizem) Dose in Kidney Disease:
- The manufacturer's labeling doesn't provide specific dosage adjustments, so caution should be exercised when using diltiazem.
- It's important to follow medical advice closely.
- Additionally, diltiazem isn't removed by either hemodialysis or peritoneal dialysis, so no supplemental dose is usually needed in patients undergoing these treatments.
Diltiazem Dose in Liver disease:
- The manufacturer's labeling doesn't include specific dosage adjustments, so it's important to use diltiazem with caution, especially in patients with liver issues.
- Diltiazem is extensively metabolized by the liver, and its half-life can be prolonged in patients with cirrhosis.
Side effects:
Note:
- Frequency ranges correspond to different dose types.
- Adverse responses may occur more frequently in patients with aberrant conduction or decreased cardiac function.
Common Side Effects of Diltiazem (Cardizem):
- Cardiovascular:
- Edema
- Central nervous system:
- Headache
Less Common Side Effects of Diltiazem (Cardizem):
- Cardiovascular:
- Atrioventricular Block
- Edema
- Bradycardia
- Hypotension
- Vasodilatation
- Extrasystoles
- Flushing
- Palpitations
- Central Nervous System:
- Dizziness
- Pain
- Nervousness
- Dermatologic:
- Skin Rash
- Endocrine & Metabolic:
- Gout
- Gastrointestinal:
- Dyspepsia
- Constipation
- Vomiting
- Diarrhea
- Local:
- Injection Site Reaction
- Neuromuscular & Skeletal:
- Weakness
- Myalgia
- Respiratory:
- Rhinitis
- Pharyngitis
- Dyspnea
- Bronchitis
- Cough
- Sinus Congest
Contraindications to Diltiazem (Cardizem):
- Diltiazem is contraindicated in individuals who have a hypersensitivity to diltiazem or any component of its formulation, as well as in those with sick sinus syndrome (except if they have a functioning artificial pacemaker), second- or third-degree atrioventricular (AV) block (except if they have a functioning artificial pacemaker), severe hypotension (systolic blood pressure <90 mm Hg), acute myocardial infarction (MI) with pulmonary congestion, or intravenous (IV) administration concurrently or within a few hours of IV beta-blockers.
- Additionally, IV diltiazem is contraindicated in cases of cardiogenic shock, atrial fibrillation or flutter associated with accessory bypass tract (such as Wolff-Parkinson-White syndrome), and ventricular tachycardia with wide-complex tachycardia (QRS ≥0.12 seconds), unless the origin is determined to be supraventricular.
- Canadian labeling adds contraindications of pregnancy, use in women of childbearing potential, concurrent use with IV dantrolene, and concurrent use with ivabradine.
Warnings and precautions
Conductivity abnormalities
- Diltiazem may lead to conduction abnormalities such as first-, second-, and third-degree atrioventricular (AV) block or sinus bradycardia.
- The risk of these abnormalities is higher when diltiazem is used with other medications known to slow cardiac conduction.
Dermatologic reactions
- Transient dermatologic reactions, though rare, can occur with the use of diltiazem.
- If such a reaction persists or worsens, it's essential to discontinue the medication.
- In severe cases, diltiazem has been associated with serious skin conditions like Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and exfoliative dermatitis.
- Immediate medical attention is necessary if any of these severe reactions are suspected.
Hepatic effects
- Diltiazem can cause mild elevations in liver enzymes like transaminases, sometimes with increases in alkaline phosphatase and bilirubin, though these often resolve on their own.
- However, in some cases, significant elevations in liver enzymes, along with signs of acute liver injury, may occur 1 to 8 weeks after starting therapy.
- These effects are typically reversible upon discontinuation of diltiazem.
- Monitoring liver function tests is important during treatment with diltiazem to detect any potential hepatic effects early.
Syncope and hypotension:
- Symptomatic hypotension, sometimes leading to fainting (syncope), is a rare but possible side effect of diltiazem.
- It's crucial to adjust the blood pressure gradually based on the patient's clinical condition to minimize the risk of hypotension-related symptoms.
Accessory bypass tract (eg, Wolff-Parkinson-White [WPW] syndrome):
- In patients with an accessory bypass tract or preexcitation syndrome like Wolff-Parkinson-White (WPW) syndrome, the use of diltiazem during an episode of atrial fibrillation or flutter can potentially increase anterograde conduction down the accessory pathway, raising the risk of ventricular fibrillation.
- Therefore, it's advised to avoid using diltiazem in such patients.
- This precaution is supported by guidelines from organizations like the American Heart Association (AHA), American College of Cardiology (ACC), and the Heart Rhythm Society (HRS).
Hepatic impairment
- Patients with hepatic impairment should use diltiazem cautiously.
Left ventricular dysfunction:
- Exercise caution when using diltiazem in patients with left ventricular dysfunction, as its negative inotropic effects may worsen the condition.
- Avoid its use in patients with heart failure, as calcium channel blockers like diltiazem have not shown benefit and may lead to worse outcomes in this population, according to recommendations from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA).
Renal impairment
- Exercise caution when prescribing diltiazem to patients with renal impairment.
Diltiazem: Drug Interaction
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
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Risk Factor C (Monitor therapy) |
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Abemaciclib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Alfentanil's serum levels may rise as a result of DilTIAZem. |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Alpha1-Blockers |
The hypotensive effects of calcium channel blockers may be strengthened. |
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Amiodarone's bradycardic action may be enhanced by calcium channel blockers (Nondihydropyridine). Sinus arrest has reportedly occurred. |
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AmLODIPine |
The serum levels of AmLODIPine may rise in response to CYP3A4 Inhibitors (Moderate). |
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Amphetamines |
May lessen the effectiveness of antihypertensive agents. |
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Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
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Apixaban's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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The serum levels of ARIPiprazole may rise in the presence of CYP3A4 Inhibitors (Moderate). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph. |
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ARIPiprazole |
ARIPiprazole's serum levels may rise in response to CYP2D6 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph. |
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Aspirin |
Nondihydropyridine, a calcium channel blocker, may increase the antiplatelet action of aspirin. |
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Atosiban |
Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk. |
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Barbiturates |
Calcium Channel Blockers' metabolic rate might be increased. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The concurrent use of phenobarbital and nimodipine is not recommended. |
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Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
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Benzhydrocodone |
The serum levels of Benzhydrocodone may rise in response to moderate CYP3A4 inhibitors. In particular, there might be an increase in hydrocodone concentration. |
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Beta-Blockers |
Nondihydropyridine, a calcium channel blocker, may increase the hypotensive effects of beta-blockers. In addition, reports of bradycardia and heart failure symptoms have been made. The serum concentration of beta-blockers may rise in response to calcium channel blockers (nondihydropyridine). Levobunolol and metipranolol are exceptions. |
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Blonanserin |
Blonanserin's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Bosentan |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
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The serum levels of bosentan may rise after taking CYP3A4 Inhibitors (Moderate). Management: It is not advised to use a CYP2C9 inhibitor and a CYP3A inhibitor concurrently, or to use a single medication that inhibits both enzymes, with bosentan because this will likely result in a significant rise in the drug's serum concentrations. Monograph for more information. |
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Bradycardia-Causing Agents |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. In patients taking AV blocking medications |
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bretylium may also strengthen atrioventricular (AV) blockade |
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Brexpiprazole |
Brexpiprazole's serum levels may rise in the presence of moderate CYP3A4 inhibitors. Treatment: If a moderate CYP3A4 inhibitor and either a strong or moderate CYP2D6 inhibitor are also used, the dose of brexpiprazole should be lowered to 25% of the regular dose. |
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Brimonidine (Topical) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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The serum content of BusPIRone may rise in response to calcium channel blockers (Nondihydropyridine). |
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Calcium Channel Blockers (Dihydropyridine) |
Possibly makes calcium channel blockers' hypotensive effects more potent (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may cause an increase in serum calcium channel blocker concentration (Dihydropyridine). |
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Calcium Salts |
May reduce calcium channel blockers' therapeutic efficacy. |
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Cannabidiol |
Cannabidiol's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Cannabis |
Cannabis serum concentrations may rise in response to moderate CYP3A4 inhibitors. Serum concentrations of cannabidiol and tetrahydrocannabinol may rise particularly. |
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Cardiac Glycosides |
The AVblocking effect of cardiac glycosides may be enhanced by calcium channel blockers (nondihydropyridine). Cardiac Glycosides' serum levels may rise in response to calcium channel blockers (Nondihydropyridine). |
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Clofazimine |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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CloNIDine |
May improve Calcium Channel Blockers' ability to inhibit AV (Nondihydropyridine). Additionally, sinus node dysfunction might be aggravated. |
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Clopidogrel |
Calcium channel blockers may reduce Clopidogrel's therapeutic efficacy. |
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Codeine |
The active metabolite(s) of codeine may be present in lower serum concentrations while taking CYP3A4 Inhibitors (Moderate). |
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Colestipol |
DilTIAZem's absorption might be decreased. |
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Copanlisib |
It's possible that DilTIAZem will raise Copanlisib's serum levels. |
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Corticosteroids (Systemic) |
The serum levels of corticosteroids may rise when using DilTIAZem (Systemic). |
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CYP3A4 Inducers (Moderate) |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
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CYP3A4 Inhibitors (Moderate) |
May slow down CYP3A4 substrate metabolism (High risk with Inhibitors). |
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CYP3A4 Substrates (High risk with Inhibitors) |
The metabolism of CYP3A4 Substrates may be decreased by moderate CYP3A4 Inhibitors (High risk with Inhibitors). Alitretinoin (Systemic), Praziquantel, Trabectedin, and Vinorelbine are exceptions. |
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May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
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Can lessen an antihypertensive drug's therapeutic impact. |
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Diazoxide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Dofetilide's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). |
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Dronabinol's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
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May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Efavirenz |
May lower the level of DilTIAZem in the serum. |
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Erdafitinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
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Erdafitinib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Erdafitinib |
P-glycoprotein/ABCB1 Substrates serum levels can rise. |
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Estrogen Derivatives |
The serum concentration of oestrogen derivatives may rise in response to moderately potent CYP3A4 inhibitors. |
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Fingolimod |
DilTIAZem could make Fingolimod's bradycardic impact more pronounced. |
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Fluconazole |
Calcium Channel Blockers' serum levels can rise. |
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Fosnetupitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Grapefruit Juice |
DilTIAZem serum concentration can rise. |
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Halofantrine |
Halofantrine's serum levels may rise in response to moderate CYP3A4 inhibitors. Management: If halofantrine is taken with mild CYP3A4 inhibitors, extreme caution and potentially increased ECG monitoring should be required. Drugs marked as exclusions from this document are covered in separate monographs on drug interactions. |
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Herbs (Hypertensive Properties) |
May lessen the effectiveness of antihypertensive agents. |
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Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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HYDROcodone |
CYP3A4 Inhibitors (Moderate) may raise the level of Hydrocodone in the blood. |
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Hypotension-Associated Agents |
The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications. |
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The active metabolite(s) of ifosfamide may be present in lower serum concentrations when CYP3A4 Inhibitors (Moderate) are used. |
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Imatinib |
Imatinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Bradycardia-Causing Substances may intensify Lacosamide's AV-blocking effects. |
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May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
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Lithium |
Nondihydropyridine, a calcium channel blocker, may increase lithium's neurotoxic effects. Nondihydropyridine, a calcium channel blocker, may raise the serum levels of lithium. With this combination, lower or unchanged lithium concentrations have also been noted. |
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Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Magnesium Salts |
Magnesium salts may become more dangerous or poisonous when calcium channel blockers are used. Magnesium salts may enhance the hypotensive effects of calcium channel blockers. |
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Manidipine |
When used with CYP3A4 Inhibitors, manidipine's serum levels could increase (Moderate). |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Mirodenafil |
The serum concentration of Mirodenafil may rise in response to CYP3A4 Inhibitors (Moderate). |
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Molsidomine |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Naftopidil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Naldemedine's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). |
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Nalfurafine |
Nalfurafine's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). |
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Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
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Neuromuscular-Blocking Agents (Nondepolarizing) |
The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing). |
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Nicergoline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Nicorandil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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NiMODipine's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications. |
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CYP3A4 Inhibitors (Moderate) may intensify OxyCODONE's harmful/toxic effects. The serum concentration of OxyCODONE may rise in response to moderately potent CYP3A4 inhibitors. The active metabolite Oxymorphone's serum concentrations could also rise. |
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May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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Perhexiline |
The quantity of perhexiline in the serum may rise in response to CYP2D6 Inhibitors (Weak). |
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P-glycoprotein/ABCB1 Inhibitors |
Pglycoprotein/ABCB1 Substrates serum levels can rise. Additionally, p-glycoprotein inhibitors may improve the distribution of pglycoprotein substrates to particular cells, tissues, and organs where high levels of p-glycoprotein are present (e.g., brain, T-lymphocytes, testes, etc.). |
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Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
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Phosphodiesterase |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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The metabolism of pimecrolimus may be decreased by moderate CYP3A4 inhibitors. |
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Propafenone's serum levels may rise when taking CYP3A4 Inhibitors (Moderate). Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book. |
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Prostacyclin Analogues |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. |
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QuiNIDine's serum levels may rise with the use of DilTIAZem. |
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Red Yeast Rice |
The blood content of Red Yeast Rice may rise in response to Calcium Channel Blockers (Nondihydropyridine). Particularly, levels of lovastatin (and perhaps other similar substances) may rise. |
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Calcium Channel Blockers' bradycardic impact might be boosted (Nondihydropyridine). |
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The serum concentration of rupatadine may rise in response to moderate CYP3A4 inhibitors. |
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Ruxolitinib |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. Management: The Canadian product labeling for roxolitinib advises against using it in conjunction with medications that can cause bradycardia whenever possible. |
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Ruxolitinib's serum concentration may rise when taken with CYP3A4 Inhibitors (Moderate). |
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CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. |
|
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may lower the level of CYP3A4 substrates in the serum (high risk with inducers). |
|
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SAXagliptin |
The serum concentration of SAXagliptin may rise in response to moderately potent CYP3A4 inhibitors. |
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The serum concentration of Sildenafil may rise in response to CYP3A4 Inhibitors (Moderate). |
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Silodosin's serum concentration may rise in response to moderate CYP3A4 inhibitors. |
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may lower CYP3A4 substrate levels in serum (high risk with inducers). |
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Tacrolimus (Systemic) |
Tacrolimus (Systemic) metabolism may be slowed down by calcium channel blockers (Nondihydropyridine). |
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Tacrolimus (Topical) |
Tacrolimus (Topical) metabolism may be slowed down by calcium channel blockers (nonhydropyridine). |
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Tamsulosin's serum concentration may rise when taken with CYP3A4 Inhibitors (Moderate). |
|
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Terlipressin |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Tetrahydrocannabinol |
Tetrahydrocannabinol's serum concentration may rise in response to moderate CYP3A4 inhibitors. |
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Serum concentrations of ticagrelor may increase in response to mild CYP3A4 inhibitors. |
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may lower the level of CYP3A4 substrates in the serum (high risk with inducers). |
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Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
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Trabectedin's serum concentration may rise in response to CYP3A4 Inhibitors (Moderate). |
|
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Udenafil |
The serum concentration of udenafil may rise in response to CYP3A4 Inhibitors (Moderate). |
|
Vilazodone's serum concentration may rise when taken with CYP3A4 Inhibitors (Moderate). |
|
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Vindesine's serum concentration may rise in response to moderate CYP3A4 inhibitors. |
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Yohimbine |
Antihypertensive Agents' ability to reduce blood pressure may be diminished. |
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The serum concentration of Zuclopenthixol may rise in response to CYP3A4 Inhibitors (Moderate). |
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Risk Factor D (Consider therapy modification) |
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Acalabrutinib |
Acalabrutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Lower the dose of acalabrutinib to 100 mg once daily while using a mild CYP3A4 inhibitor. If there is any concurrent use, keep a watchful eye on the patient for both acalabrutinib response and signs of side effects. |
|
Amifostine |
Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications. Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine is administered when used at chemotherapeutic doses. Amifostine should not be given if blood pressure lowering treatment cannot be stopped. |
|
Antifungal Agents (Azole Derivatives, Systemic) |
Calcium Channel Blockers' harmful or toxic effects could be exacerbated. In particular, itraconazole may make verapamil or diltiazem's unfavourable inotropic effects worse. Calcium Channel Blockers' metabolism may be slowed down by antifungal agents (systemic azole derivatives). Fluconazole and isavuconazonium, which are covered in different monographs, probably have less powerful effects than those of other azoles. Treatment: Itraconazole should not be used concurrently with felodipine or nisoldipine. With any such combination, regular monitoring is advised; calcium channel blocker dose decreases might be necessary. Fluconazole and isavuconazonium sulphate are exceptions. |
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AtorvaSTATin |
DilTIAZem serum concentration can rise. AtorvaSTATin serum levels could be elevated by DilTIAZem. When taken with diltiazem, management should take into account using lower atorvastatin doses. |
|
Avanafil |
Avanafil's serum levels may rise in response to moderate CYP3A4 inhibitor therapy. Management: When used with a mild CYP3A4 inhibitor, the maximum adult dose of avanafil is 50 mg per 24 hours. Additionally, patients receiving this combination should be watched more attentively for signs of side effects. |
|
Brigatinib |
Brigatinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: When possible, avoid taking brigatinib at the same time as mild CYP3A4 inhibitors. Reduce the dose of brigatinib by around 40% if such a combination cannot be avoided (i.e., from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 |
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The serum levels of bromocriptine may rise in response to moderately potent CYP3A4 inhibitors. Treatment: When used with a mild CYP3A4 inhibitor, the daily dose of bromocriptine should not exceed 1.6 mg. Other bromocriptine medicines do not give as detailed advice as the Cycloset brand does regarding dose restriction. |
|
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Budesonide (Topical) |
The serum concentration of Budesonide may rise while using moderate amounts of CYP3A4 inhibitors (Topical). Management: Avoid this combination, according to US prescribing advice. Canadian goods labels do not expressly advise against anything. If used in conjunction, keep an eye out for too glucocorticoid effects as budesonide exposure may rise. |
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The serum levels of CarBAMazepine may rise in response to calcium channel blockers (Nondihydropyridine). Calcium Channel Blockers' serum levels may be reduced by carbamazepine (Nondihydropyridine). Treatment: When starting nondihydropyridine calcium channel blockers, take into consideration reducing the dose of carbamazepine on an as-needed basis. Keep an eye out for carbamazepine's increased toxicity and the calcium channel blocker's diminished therapeutic benefits. |
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Ceritinib |
Bradycardia-Causing Agents may intensify Ceritinib's bradycardic impact. Management: If this combination cannot be avoided, continuously monitor patients' blood pressure and heart rate throughout therapy and look for any signs of symptomatic bradycardia in them. A separate monograph is dedicated to discussing exceptions. |
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Cilostazol's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). Management: When treating adult patients who are already using mild CYP3A4 inhibitors, think about lowering the dose of cilostazol to 50 mg twice daily. |
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Calcium Channel Blockers' serum levels can rise. Management: Take cimetidine substitutes into consideration. If there is no suitable substitute, watch for increased calcium channel blocker effects after starting or increasing the dosage of cimetidine and decreased effects after stopping or decreasing the dosage. |
|
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CycloSPORINE (Systemic) |
Nondihydropyridine, a calcium channel blocker, may slow the metabolism of cycloSPORINE (Systemic). Calcium Channel Blockers may have slower metabolism when CycloSPORINE (Systemic) is taken (Nondihydropyridine). |
|
CYP3A4 Inducers (Strong) |
May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label. |
|
CYP3A4 Inhibitors (Strong) |
May slow down CYP3A4 substrate metabolism (High risk with Inhibitors). |
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May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects). |
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Dapoxetine |
Dapoxetine's serum levels may rise in response to moderate CYP3A4 inhibitors. Treatment: When used with a mild CYP3A4 inhibitor, the daily dose of dapoxetine should be restricted to 30 mg. |
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The active metabolite(s) of Deflazacort may be present in higher serum quantities when taking CYP3A4 Inhibitors (Moderate). When taking deflazacort with a strong or moderate CYP3A4 inhibitor, only take one-third of the prescribed dose. |
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DOXOrubicin (Conventional) |
The serum concentration of DOXOrubicin may rise after using moderate amounts of CYP3A4 inhibitors (Conventional). Treatment: Whenever possible, avoid using mild CYP3A4 inhibitors in patients receiving doxorubicin. Pfizer Inc., a U.S. manufacturer, advises against using certain mixtures. |
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Dronedarone |
The AV-blocking activity of dronedarone may be enhanced by calcium channel blockers (nondihydropyridine). Dronedarone may have more electrophysiologic effects overall. The serum concentration of dronedarone may rise in response to calcium channel blockers (nondihydropyridine). Calcium Channel Blockers' serum levels may rise in response to dronedarone (Nondihydropyridine). Management: Verapamil and diltiazem are examples of nondihydropyridine calcium channel blockers that should be used at lower starting dosages. Calcium channel blocker dosage should only be increased after receiving ECG-based confirmation that the combination is well-tolerated. |
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Eletriptan's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Eletriptan shouldn't be taken within 72 hours of a moderate CYP3A4 inhibitor. |
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Eliglustat's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: There are specific situations when use should be avoided. For information, consult the entire medication interaction monograph. |
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Encorafenib |
Encorafenib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Whenever possible, refrain from taking moderate CYP3A4 inhibitors and encorafenib concurrently. Reduce the encorafenib dose to 50% of the encorafenib dose used prior to starting the CYP3A4 inhibitor if concurrent administration is unavoidable. |
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May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. |
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Eplerenone's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). Management: Depending on the indication and foreign labelling, different doses of eplerenone should be used concurrently with mild CYP3A4 inhibitors. For information, consult the entire medication interaction monograph. |
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Esmolol |
Esmolol's bradycardic action may be enhanced by calcium channel blockers (nondihydropyridine). Management: Giving one medication while the effects of the other are still present is not advised when giving IV verapamil or diltiazem with esmolol. Esmolol is labelled as contraindicated for usage if taken within 24 hours in Canada. |
|
Everolimus |
CYP3A4 Inhibitors (Moderate) may raise the level of Everolimus in the blood. For the majority of cases, everolimus dose decreases are necessary. For detailed dose modification and monitoring suggestions, consult the full monograph or prescription information. |
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FentaNYL |
The serum levels of FentaNYL may rise in response to CYP3A4 Inhibitors (Moderate). Management: After starting this combination, keep a watchful eye on the patients for a few days and alter the fentanyl dosage as necessary. |
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Calcium channel blockers may raise the level of fosphenytoin in the blood. Monitoring for phenytoin toxicity while using a calcium channel blocker (CCB) at the same time or reduced phenytoin effects while stopping the CCB are the two management options. Check for diminished therapeutic effects of CCB. The Canadian labelling for nimodipine specifically forbids the use of phenytoin. |
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GuanFACINE |
CYP3A4 Inhibitors (Moderate) may raise the level of GuanFACINE in the serum. When starting this combo, cut the guanfacine dose in half. |
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Ibrutinib |
Ibrutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: While paired with mild CYP3A4 inhibitors, reduce ibrutinib dosage to 280 mg per day when treating B-cell malignancies. When treating graft versus host disease, keep a close eye on the patients and adjust the ibrutinib dosage as necessary based on side effects. |
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Colchicine |
Colchicine's serum levels may rise after taking CYP3A4 Inhibitors (Moderate). Management: Increase monitoring for colchicine-related toxicity and decrease colchicine dose as advised when used with a moderate CYP3A4 inhibitor. For information, see the entire monograph. Patients with weakened liver or kidney function should be treated with extreme caution. |
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Ivacaftor |
Ivacaftor's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Ivacaftor dosage reductions are necessary; for complete monograph material and specific recommendations based on age and weight. |
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Ivosidenib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Whenever feasible, refrain from combining ivosidenib with mild CYP3A4 inhibitors. Watch out for increased ivosidenib toxicity if taken in combination. Drugs that are specifically mentioned as exceptions are covered in further detail in their own drug interaction monographs. |
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Lorlatinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes. |
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Lovastatin |
DilTIAZem serum concentration can rise. Lovastatin's serum levels may rise as a result of DilTIAZem. Treatment: In patients on diltiazem, start lovastatin at a maximum adult dose of 10 mg/day and do not go over 20 mg/day. Keep an eye out for warnings. |
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Lurasidone |
Lurasidone's serum levels may rise in response to moderate CYP3A4 inhibitors. Treatment: According to the US labelling for lurasidone, the dose should be cut in half and used with a mild CYP3A4 inhibitor. Some non-US labelling advises starting with 20 mg/day of lurasidone and limiting the dosage to 40 mg/day; concurrent use of grapefruit products should be avoided. |
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Macrolide Antibiotics |
Calcium Channel Blockers' metabolic rate might be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Azithromycin (Systemic), Fidaxomicin, Roxithromycin, and Spiramycin are exceptions. |
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Midostaurin |
Midostaurin's serum concentration may rise as a result of DilTIAZem. Management: If at all possible, look for alternatives to taking diltiazem and midostaurin together. If concurrent use cannot be avoided, keep an eye on the patients' risk of adverse responses increasing. |
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May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided. |
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May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified. |
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The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished. |
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Olaparib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: If at all feasible, refrain from administering mild CYP3A4 inhibitors to patients receiving olaparib. Olaparib dosage should be decreased to 150 mg twice daily if such concomitant use cannot be avoided. |
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The serum levels of phenytoin may rise when calcium channel blockers are used. Calcium Channel Blockers' serum levels may be reduced by phenytoin. Avoid combining nimodipine or nifedipine with phenytoin for management. With any concurrent use, keep an eye out for phenytoin toxicity and/or diminished calcium channel blocker effects. |
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May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Pitolisant should not be used in conjunction with a CYP3A4 substrate that has a limited therapeutic index. Additional CYP3A4 substrates need to be closely watched. |
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Protease Inhibitors |
Calcium Channel Blockers' metabolism might be slowed down (Nondihydropyridine). The risk of AV nodal blockage may rise with higher calcium channel blocker serum concentrations. Management: When feasible, avoid concurrent use. Check for CCB toxicity if used. Atazanavir's producer advises that a dose reduction of 50% for diltiazem be taken into consideration. Use of bepridil and saquinavir, tipranavir, and darunavir/cobicistat is not advised. |
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Ranolazine |
The serum concentration of Ranolazine may rise in response to Calcium Channel Blockers (Nondihydropyridine). When used with diltiazem or verapamil, the dose of ranolazine should be restricted to no more than 500 mg twice daily. |
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Ranolazine's serum levels may rise after taking CYP3A4 Inhibitors (Moderate). Treatment: In patients receiving mild CYP3A4 inhibitors concurrently, the adult ranolazine dose should be restricted to no more than 500 mg twice daily (e.g., diltiazem, verapamil, erythromycin, etc.). |
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Rifamycin Derivatives |
May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. |
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May increase the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg/day and diltiazem 240 mg/day; avoid Simcor (simvastatin/niacin) because fixed simvastatin doses exceed the maximum. |
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The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility. |
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Siponimod's bradycardic action may be enhanced by bradycardia-causing substances. Management: Steer clear of combining siponimod with medications that can slow your heart rate. |
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The serum concentration of Sirolimus may rise after taking CYP3A4 Inhibitors (Moderate). Management: If sirolimus is taken with a mild CYP3A4 inhibitor, keep an eye out for elevated serum concentrations. Lower starting dosages of sirolimus or dose reductions of sirolimus will probably be needed. |
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Sonidegib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Whenever possible, refrain from taking moderate CYP3A4 inhibitors and sonidegib concurrently. Reduce the duration of CYP3A4 inhibitor use to less than 14 days when concurrent use cannot be avoided. |
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St John's Wort |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label. |
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May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation. |
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Suvorexant's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Suvorexant is administered at a dose of 5 mg per day to patients who are on a mild CYP3A4 inhibitor. If more dosage is required for effectiveness, the maximum amount per day is 10 mg. |
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Tezacaftor |
Tezacaftor's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Tezacaftor/ivacaftor (100 mg/150 mg) should be administered in the morning, every other day, when taken with mild CYP3A4 inhibitors. Every other day, in the morning, on the days that tezacaftor and ivacaftor are given alternately, ivacaftor (150 mg) alone should be administered. |
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Tolvaptan's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). Management: When used with a mild CYP3A4 inhibitor, jynarque dosage must be adjusted. For more detailed advice, consult the complete interaction monograph or labelling. Samsca use should generally be avoided when moderate CYP3A4 inhibitors are present. |
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Venetoclax's serum levels may rise in response to moderate CYP3A4 inhibitors. Management: In patients who need these combinations, lower the dose of venetoclax by at least 50%. |
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Zopiclone |
Zopiclone's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: If taken with a mild CYP3A4 inhibitor, the first adult dose of zopiclone shouldn't be more than 3.75 mg. If these medications are taken together, patients should be kept an eye out for any zopiclone toxicity symptoms. |
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Risk Factor X (Avoid combination) |
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Aprepitant's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Asunaprevir |
Asunaprevir's serum levels may rise in response to moderate CYP3A4 inhibitor therapy. |
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Bosutinib |
Bosutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Bromperidol |
The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol. |
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Budesonide (Systemic) |
The serum concentration of Budesonide may rise while using moderate amounts of CYP3A4 inhibitors (Systemic). |
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Cobimetinib |
Cobimetinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Steer clear of combining cobimetinib with mild CYP3A4 inhibitors. Reduce the dosage of cobimetinib to 20 mg per day if concomitant short-term (14 days or less) use cannot be avoided. |
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Conivaptan |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Dantrolene |
May make calcium channel blockers' hyperkalemic impact stronger (Nondihydropyridine). Dantrolene may intensify Calcium Channel Blockers' adverse inotropic impact (Nondihydropyridine). Management: Only intravenous dantrolene administration has been used to characterise this interaction. |
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Domperidone |
Domperidone's serum levels may rise in response to moderate CYP3A4 inhibitors. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book. |
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Flibanserin's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Fosaprepitant |
Fosaprepitant's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Fusidic Acid (Systemic) |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Idelalisib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
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Ivabradine |
Ivabradine's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Ivabradine |
The bradycardic effect of ivabradine may be enhanced by calcium channel blockers (nonhydropyridine). Ivabradine may increase Calcium Channel Blockers' ability to extend QTc (Nondihydropyridine). Particularly, bepridil's QTc prolonging effects might be improved. The serum levels of Ivabradine may rise in response to calcium channel blockers (Nondihydropyridine). Particularly, serum ivabradine concentrations may rise in response to verapamil or diltiazem. |
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Lomitapide |
Lomitapide's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Naloxegol |
Naloxegol's serum levels may rise in response to moderately potent CYP3A4 inhibitors. |
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Neratinib |
Neratinib's serum levels may rise in response to moderate CYP3A4 inhibitors. |
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Pimozide's serum levels may rise after taking CYP3A4 Inhibitors (Moderate). |
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May lower the level of DilTIAZem in the serum. |
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Simeprevir |
Simeprevir's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). |
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Ulipristal |
Ulipristal's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: This is specific to the use of ulipristal for indications or symptoms of uterine fibroids (Canadian indication). When ulipristal is administered to patients as an emergency contraception, they should be watched closely for ulipristal toxicity. |
Monitoring parameters:
- Liver Function Tests: Regular monitoring of liver function tests is advisable due to the potential for hepatic effects.
- Kidney Function: Patients with renal impairment should be closely monitored when using diltiazem.
- Blood Pressure: Continuous monitoring of blood pressure is essential, especially in hypertensive patients.
- ECG: Periodic ECG monitoring may be necessary to assess cardiac function and conduction.
- Heart Rate: Monitoring of heart rate is crucial, particularly in patients with atrial fibrillation or flutter for ventricular rate control.
Ventricular Rate Control in Atrial Fibrillation or Flutter
- Patients who respond to diltiazem typically exhibit:
- At least a 20% decrease in ventricular response rate.
- Ventricular rate <100 beats per minute.
Hypertension Management Guidelines
ACC/AHA Guidelines (Whelton 2017):
- Confirmed Hypertension with Known Cardiovascular Disease (CVD) or 10-Year ASCVD Risk ≥10%:
- Target blood pressure <130/80 mm Hg is recommended.
- Confirmed Hypertension without Markers of Increased ASCVD Risk:
- Target blood pressure <130/80 mm Hg may be reasonable.
American Diabetes Association (ADA) Guidelines (ADA 2018):
- Patients ≥18 to ≤65 Years:
- Goal of therapy: SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 to ≤65 Years at High Risk of Cardiovascular Disease:
- Goal of therapy: SBP <130 mm Hg and DBP <80 mm Hg (if achievable without undue treatment burden).
- Patients ≥65 Years (Healthy or Complex/Intermediate Health):
- Goal of therapy: SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥65 Years (Very Complex/Poor Health):
- Goal of therapy: SBP <150 mm Hg and DBP <90 mm Hg.
How to administer Diltiazem (Cardizem)?
Oral Administration:
- Immediate Release Tablet (e.g., Cardizem):
- Take before meals and at bedtime.
- Swallow the tablet whole; do not split, crush, or chew unless directed otherwise by the manufacturer.
- Crushing immediate-release tablets may affect how the medication works, except for those made using a direct compression technique, which can be crushed. Brands like Cardizem allow crushing.
- Long-Acting Dosage Forms (e.g., Cardizem CD, Cardizem LA, Cartia XT, Matzim LA):
- Swallow whole; do not open, chew, or crush.
- Administer at the same time each day, either morning or evening.
- Cardizem XR should be taken on an empty stomach in the morning.
- Taztia XT and Tiazac capsules may be opened and sprinkled on applesauce, which should be swallowed without chewing, followed by drinking water.
- Tiazac XC (Canadian product) should be administered at bedtime.
Intravenous (IV) Administration:
- Bolus Doses:
- Given over 2 minutes with continuous ECG and blood pressure monitoring.
- Continuous Infusion:
- Administer via infusion pump.
- Increase infusion rate in 5 mg/hour increments as needed, up to a maximum of 15 mg/hour.
- Response to bolus doses may take several minutes to reach maximum effect and may persist for several hours after infusion is stopped.
Mechanism of action of Diltiazem (Cardizem):
- Diltiazem works by blocking calcium ions from entering specific areas of vascular smooth muscle and myocardium during depolarization.
- This action leads to relaxation of coronary vascular smooth muscle and dilation of coronary arteries, which increases the delivery of oxygen to the heart muscle.
- This mechanism is particularly beneficial for patients with vasospastic angina, helping to alleviate symptoms by improving myocardial oxygen supply.
Onset of action:
- Oral Immediate Release Tablet: 30 to 60 minutes.
- IV Bolus: 3 minutes.
Duration:
- IV Bolus: 1 to 3 hours.
- Continuous Infusion (after discontinuation): 0.5 to 10 hours.
Absorption:
- Oral Immediate Release Tablet: Approximately 98%.
- Extended Release Capsule: Approximately 93% to >95%.
Distribution:
- Volume of Distribution: 3 to 13 L/kg.
- Protein Binding: 70% to 80%.
Metabolism:
- Hepatic metabolism via CYP-450 and conjugation.
- Forms metabolites: N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-Nmonodesmethyldiltiazem, desacetylO-desmethyldiltiazem, and desacetyl-N, O-desmethyldiltiazem.
- Plasma concentrations of some metabolites may accumulate following continuous infusion.
Bioavailability:
- Oral: Approximately 40% due to extensive first-pass metabolism.
Half-life Elimination:
- Immediate Release Tablet: 3 to 4.5 hours.
- Extended Release Tablet: 6 to 9 hours.
- Extended Release Capsule: 4 to 9.5 hours.
- IV Single Dose: Approximately 3.4 hours.
- Continuous Infusion: 4 to 5 hours.
Time to Peak Serum Concentration:
- Immediate Release Tablet: 2 to 4 hours.
- Extended Release Tablet: 11 to 18 hours.
- Extended Release Capsule: 10 to 14 hours.
Excretion:
- Mostly via urine (2% to 4% as unchanged drug); also excreted in feces.
International Brand Names of Diltiazem:
- Cardizem
- Cardizem CD
- Cardizem LA
- Cartia XT
- Dilt-XR
- dilTIAZem CD
- Matzim LA
- Taztia XT
- Tiazac
- ACT Diltiazem CD
- ACT Diltiazem T
- APO-Diltiaz
- APO-Diltiaz CD
- APO-Diltiaz SR
- APO-Diltiaz TZ
- Cardizem CD
- Diltiazem CD
- Diltiazem TZ
- Diltiazem-CD
- MAR-Diltiazem T
- NU-Diltiaz-SR
- Pharma-Diltiaz
- PMS-Diltiazem CD
- SANDOZ Diltiazem CD
- SANDOZ Diltiazem T
- TEVA-Diltazem
- TEVA-Diltiazem CD
- TEVA-Diltiazem HCl ER
- Tiazac
- Tiazac XC
- TRIA-Diltiazem
- Acalix
- Adizem
- Adizem XL
- Adizem-CD
- Adizem-XL
- Aldizem
- Altiazem
- Altiazem Retard
- Altiazem RR
- Andico
- Angiodrox
- Angiotrofen
- Angiotrofin
- Angiotrofin Retard
- Angiozem
- Angitect
- Angizem
- Apo-diltiazem CD
- Balcor
- Beatizem
- Bi-Tildiem
- Blocalcin
- Calcicard
- Calnurs
- Cardiazem
- Cardil
- Cardil Retard
- Cardium
- Cardizem
- Cardizem CD
- Cardizem Retard
- Cardizem SR
- Cardizem Unotard
- Cordila SR
- Cordizem
- Corzem
- Dasav
- Dazil
- Deltazen
- Denazox
- Diacor LP
- Diacordin
- Diladel
- Dilatam
- Dilatam 120 SR
- Dilatam 240 CD
- Dilatame
- Dilbres
- Dilcardia
- Dilconton XL-120
- Dilcor
- Dilem SR
- Dilfar
- Dilrene
- Dilta-Hexal
- Diltahexal
- Diltam
- Diltan
- Diltan SR
- Diltelan
- Diltelan Depot
- Dilteran SR
- Diltiazem-B
- DiltiazemEthypharm
- Diltiazem-Xl
- Diltiazyn
- Diltime
- Dilzanton
- Dilzem
- Dilzem LA
- Dilzem Retard
- Dilzem RR
- Dilzem SR
- Dilzene
- Dilzereal 90 Retard
- Dilzicardin
- Dinisor Retard
- DTM
- Entrydil
- Ergolan
- Gadoserin
- Hagen
- Hart
- Helsibon
- Herben
- Herbesser
- Herbesser 180 SR
- Herbesser 60
- Herbesser 90 SR
- Herbesser R100
- Herbesser R200
- Herbessor
- Herbessor 30
- Heresser 90SR
- Hesor
- Incoril
- Iski
- Kaizem CD
- Lytelsen
- Masdil
- Metazem
- MonoTildiem
- Mono-Tildiem SR
- Monotildiem
- Myonil
- Myonil Retard
- Neocard
- Pazeadin
- Progor
- Riazem
- Surazem
- Telzim
- Tiadil
- Tilazem
- Tilazem 90
- Tildiem
- Tildiem CR
- Tildiem LA
- Tildiem Retard
- Tizem
- Vasocardol CD
- Zaldem
- Zandil
- Zemtrial
- Ziruvate
Diltiazem Brand Names in Pakistan:
|
Diltiazem (Hcl) Tablets 30 Mg in Pakistan |
|
|
Anglozem |
Euro Pharma International |
|
Calzem |
Efroze Chemical Industries (Pvt) Ltd. |
|
Carezem |
Tg Pharma |
|
Deltazem |
Delta Pharma (Pvt) Ltd. |
|
Desbon |
Evron (Pvt) Ltd. |
|
Di-Zone |
Wns Field Pharmaceuticals |
|
Dilcare |
Valor Pharmaceuticals |
|
Dilit |
Geofman Pharmaceuticals |
|
Diltiazaf |
Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
|
Dilzem |
Pfizer Laboratories Ltd. |
|
Dtz |
Ferozsons Laboratoies Ltd. |
|
Etizem |
Ici Pakistan Ltd. |
|
Eurozem |
Euro Pharma International |
|
Herbesser |
Highnoon Laboratories Ltd. |
|
Locard |
Akbar Brothers. |
|
Metazem |
Mass Pharma (Private) Limited |
|
Tiazem |
Hilton Pharma (Pvt) Limited |
|
Vascozem |
Zinta Pharmaceuticals Industries |
|
Zem |
Saydon Pharmaceutical Industries (Pvt) Ltd. |
|
Diltiazem (Hcl) Tablets 60 Mg in Pakistan |
|
|
Anglozem |
Euro Pharma International |
|
Calcard |
Abbott Laboratories (Pakistan) Limited. |
|
Calcicor |
Pliva Pakistan (Pvt) Limited |
|
Carezem |
Tg Pharma |
|
Desbon |
Evron (Pvt) Ltd. |
|
Di-Zone |
Wns Field Pharmaceuticals |
|
Dilcare |
Valor Pharmaceuticals |
|
Dilit |
Geofman Pharmaceuticals |
|
Diltiazaf |
Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
|
Dilzem |
Pfizer Laboratories Ltd. |
|
Dtz |
Ferozsons Laboratoies Ltd. |
|
Etizem |
Ici Pakistan Ltd. |
|
Eurozem |
Euro Pharma International |
|
Herbesser |
Highnoon Laboratories Ltd. |
|
Locard |
Akbar Brothers. |
|
Metazem A |
Mass Pharma (Private) Limited |
|
Myozem |
Fynk Pharmaceuticals |
|
Quzem |
Novartis Pharma (Pak) Ltd |
|
Tiazem |
Hilton Pharma (Pvt) Limited |
|
Vascozem |
Zinta Pharmaceuticals Industries |
|
Zem |
Saydon Pharmaceutical Industries (Pvt) Ltd. |
|
Diltiazem (Hcl) Tablets 90 Mg in Pakistan |
|
|
Calzem Forte |
Maple Pharmaceuticals (Pvt) Ltd |
|
Dilcare |
Valor Pharmaceuticals |
|
Dilzem Retard |
Pfizer Laboratories Ltd. |
|
Diltiazem (Hcl) Tablets 120 Mg in Pakistan |
|
|
Lacerol |
Atco Laboratories Limited |
|
Diltiazem (Hcl) Tablets SR 60 Mg in Pakistan |
|
|
Calzem |
Efroze Chemical Industries (Pvt) Ltd. |
|
Diltiazem (Hcl) Tablets SR 90 Mg in Pakistan |
|
|
Diltiazaf |
Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
|
Locard |
Akbar Brothers. |
|
Perlita |
Wilshire Laboratories (Pvt) Ltd. |
|
Diltiazem (Hcl) Tablets SR 120 Mg in Pakistan |
|
|
Calzem Forte |
Maple Pharmaceuticals (Pvt) Ltd |
|
Diltiazem (Hcl) Tablets SR 180 Mg in Pakistan |
|
|
Dilzem |
Pfizer Laboratories Ltd. |
|
Diltiazem (Hcl) Capsules SR 90 Mg in Pakistan |
|
|
Etizem |
Ici Pakistan Ltd. |
|
Herbesser |
Highnoon Laboratories Ltd. |
|
Diltiazem (Hcl) Capsules SR 180 Mg in Pakistan |
|
|
Herbesser |
Highnoon Laboratories Ltd. |
|
Perlita |
Wilshire Laboratories (Pvt) Ltd. |
