Chemical formula: C₂₇H₃₈N₂O₄ Molecular mass: 454.602 g/mol PubChem compound: 2520
Verapamil interacts in the following cases:
St. John’s Wort may reduce the plasma concentrations of verapamil.
In vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inducers of CYP3A4 that have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.
In vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride.
Verapamil has been shown to increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.
The combination of verapamil and antiarrhythmic agents may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).
Intravenous beta-blockers should not be given to patients under treatment with verapamil.
Verapamil may increase the plasma concentrations atorvastatin, lovastatin and simvastatin.
Treatment with HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin or lovastatin) in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g. simvastatin, atorvastatin or lovastatin), consider a reduction in the statin dose and retitrate against serum cholesterol concentrations.
Atorvastatin has been shown to increase verapamil levels. Although there is no direct in vivo clinical evidence, there is strong potential for verapamil to significantly affect atorvastatin pharmacokinetics in a similar manner to simvastatin or lovastatin. Consider using caution when atorvastatin and verapamil are concomitantly administered.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 and are less likely to interact with verapamil.
Sulfinpyrazone may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect.
When used concomitantly, inhalation anaesthetics and calcium antagonists, such as verapamil hydrochloride, should each be titrated carefully to avoid additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).
Concomitant use of verapamil with acetylsalicylic acid may increase the risk of bleeding.
Verapamil may increase the plasma concentrations of almotriptan.
Verapamil may increase the plasma concentrations of buspirone.
Verapamil may increase the plasma concentrations of carbamazepine. This may produce side effects such as diplopia, headache, ataxia or dizziness.
Verapamil may increase the plasma concentrations of ciclosporin, everolimus, sirolimus and tacrolimus which could lead to increased side-effects.
Cimetidine increases serum levels of verapamil.
Clarithromycin may increase the plasma concentrations of verapamil.
Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (P-gp). Verapamil is known to inhibit CYP3A and P-gp. When verapamil and colchicine are administered together, inhibition of P-gp and/or CYP3A by verapamil may lead to increased exposure to colchicine. Combined use is not recommended.
When oral verapamil was co-administered with dabigitran etexilate (150mg), a P-gp substrate, the Cmax and AUC of dabigatran were increased but magnitude of this change differs depending on time between administration and the formulation of verapamil. When verapamil 120mg immediate-release was co-administered one hour before a single dose of dabigatran etexilate, the dabigatran Cmax was increased by about 180% and AUC by about 150%. No meaningful interaction was observed when verapamil was administered 2 hours after dabigatran etexilate (increase of Cmax by about 10% and AUC by about 20%).
Close clinical surveillance is recommended when verapamil is combined with dabigatran etexilate and particularly in the occurrence of bleeding, notably in patients having a mild to moderate renal impairment.
Concomitant use of verapamil with intravenous dantrolene may cause hypotension, myocardial depression, and hyperkalaemia. This combination should be avoided.
Verapamil has been shown to increase the serum concentration of digoxin and caution should therefore be exercised with regard to digitalis toxicity.
Verapamil may increase the plasma concentrations of doxorubicin.
Erythromycin may increase the plasma concentrations of verapamil.
Verapamil may slightly decrease the plasma clearance of flecainide whereas flecainide has no effect on the verapamil plasma clearance.
Verapamil may increase the plasma concentrations of glibenclamide (glyburide).
Verapamil may increase the plasma concentrations of imipramine.
Serum levels of lithium may be reduced (pharmacokinetic effect). There may be increased sensitivity to lithium causing enhanced neurotoxicity (pharmacodynamic effect).
Verapamil may increase the plasma concentrations of metoprolol which may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).
Verapamil may increase the plasma concentrations of midazolam.
Reduced serum levels of verapamil when taken with phenobarbital.
Verapamil may increase the plasma concentrations of phenytoin.
Reduced serum levels of verapamil when taken with phenytoin.
Verapamil may increase the plasma concentrations of prazosin and terazosin which may have an additive hypotensive effect.
Verapamil may increase the plasma concentrations of propranolol which may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).
Verapamil may increase the plasma concentrations of quinidine. Pulmonary oedema may occur in patients with hypertrophic cardiomyopathy.
Reduced serum levels of verapamil when taken with rifampicin.
Due to the metabolic inhibitory potential of some of the HIV antiviral agents, such as ritonavir, plasma concentrations of verapamil may increase. Caution should be used or dose of verapamil may be decreased.
Telithromycin may increase the plasma concentrations of verapamil.
Verapamil may increase the plasma concentrations of theophylline which could lead to increased side-effects.
Verapamil is not removed during dialysis.
Verapamil may affect impulse conduction and should therefore be used with caution in patients with first degree AV block.
Verapamil use with caution in the presence of diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).
Animal studies have shown no teratogenic effect. Verapamil should not be administered during pregnancy unless, in the clinicians judgement, it is essential for the welfare of the patient. The possibility that verapamil can cause relaxation of the uterine muscle should be considered at term.
Verapamil is excreted in breast milk at concentrations approximately equal to 0.5-1.0 times that coexisting in maternal plasma. However, the amount ingested in such circumstances is less than 1% of the recommended therapeutic infant dose, assuming normal suckling rates.
Depending on individual susceptibility, the patient’s ability to drive a vehicle, operate machinery or work under hazardous conditions may be impaired. This is particularly true in the initial stages of treatment, when changing over from another drug or when the dose is raised. Like many other common medicines, verapamil has been shown to increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.
None stated.
Immune system disorders: allergic reactions (e.g. erythema, pruritus, urticaria) are very rarely seen.
Nervous system disorders: headaches occur rarely, dizziness, paraesthesia, tremor, extrapyramidal syndrome (e.g. parkinsonism), dystonia.
Ear and labyrinth disorders: vertigo, tinnitus.
Cardiac disorders: bradycardic arrhythmias such as sinus bradycardia, sinus arrest with asystole, 2nd and 3rd degree AV block, bradyarrhythmia in atrial fibrillation, palpitations, tachycardia, development or aggravation of heart failure, hypotension.
Vascular disorders: flushing, peripheral oedema.
Gastrointestinal disorders: nausea, vomiting, constipation is not uncommon, ileus and abdominal pain/discomfort. Gingival hyperplasia may very rarely occur when the drug is administered over prolonged periods. This is fully reversible when the drug is discontinued.
Skin and subcutaneous tissue disorders: alopecia, ankle oedema, Quincke’s oedema, Steven-Johnson syndrome, erythema multiforme, erythromelalgia, purpura.
Musculoskeletal and connective tissue disorders: muscular weakness, myalgia and arthralgia.
Reproductive system and breast disorders: impotence (erectile dysfunction) has been rarely reported and isolated cases of galactorrhoea. Gynaecomastia was observed on very rare occasions in elderly male patients under longer term verapamil treatment which was fully reversible in all cases when the drug was discontinued.
General disorders and administration site conditions: fatigue.
Investigations: On very rare occasions, a reversible impairment of liver function characterised by an increase in transaminases and/or alkaline phosphatase, may occur during verapamil treatment and is most probably a hypersensitivity reaction.
Adverse events observed in clinical trials are depicted in the following list. Within each system organ class, the adverse drug reactions are ranked under headings of frequency, using the following convention: common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports.
Common: dizziness, headache
Common: bradycardia, hypotension
Uncommon: tachycardia
Uncommon: nausea, abdominal pain
Cases of seizures during verapamil hydrochloride injection have been reported.
In rare cases of hypersensitivity, bronchospasm accompanied by pruritis and urticaria has been reported.
Other adverse events reported with verapamil are listed below by system organ class:
Psychiatric disorders: on rare occasions, nervousness has been reported.
Nervous system disorders: somnolence and extrapyramidal syndrome.
Ear and labyrinth disorders: vertigo.
Cardiac disorders/vascular disorders: decreased myocardial contractility has been reported. On rare occasions, 2nd and 3rd block may occur and in extreme cases, this may lead to asystole. The asystole is usually of short duration and cardiac action returns spontaneously after a few seconds, usually in the form of sinus rhythm. If necessary, the procedures for the treatment of overdosage should be followed as described below. On rare occasions, flushing has been reported.
Gastrointestinal disorders: gingival hyperplasia may occur very rarely when the drug is administered over prolonged periods, and is fully reversible when the drug is discontinued. On rare occasions, vomiting has also been reported.
Skin and subcutaneous tissue disorders: Steven-Johnson syndrome, erythema and hyperhidrosis.
Reproductive system and breast disorders: On very rare occasions, gynaecomastia has been observed in elderly male patients under long-term verapamil treatment; this was fully reversible in all cases when the drug was discontinued.
Investigations: A reversible impairment of liver function characterized by an increase of transaminase and/or alkaline phosphatase may occur on very rare occasions during verapamil treatment and is most probably a hypersensitivity reaction.
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