Ikapress

/ Teva

Ikapress tablets should be administered with food. Ikapress tablets can be divided (tablets are scored). They should not be chewed, sucked or crushed.
Hypertension: Dosage should be individualized by titration.
Therapy may be initiated with 1 Ikapress SR 180 mg tablet given in the morning. Lower initial doses of 120 mg (1/2 an Ikapress SR 240 mg tablet) a day may be warranted in patients who may have an increased response to verapamil (e.g. the elderly or small people). Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 hours after dosing.
The antihypertensive effects of Ikapress are evident within the first week of therapy. If adequate therapeutic response is not obtained with Ikapress 180 mg, upward dosage titration is recommended as follows:
1 Ikapress SR 240 mg tablet in the morning.
1 Ikapress SR 180 mg tablet in the morning and 1 Ikapress SR 180 mg tablet in the evening, or 1 Ikapress SR 240 mg tablet in the morning and 1/2 an Ikapress SR 240 mg tablet in the evening.
Ikapress SR 240 mg tablet every 12 hours, morning and evening. When switching from immediate-release Ikacor tablets to sustained- release Ikapress tablets, the total daily dose of verapamil in milligrams may remain the same.
Angina Pectoris: 1 Ikapress SR 240 mg tablet twice daily. Some patients may respond to a lower dosage. In such cases 1 Ikapress SR 180 mg tablet twice daily, or 1 Ikapress SR 240 mg tablet once daily may be sufficient.
For full details see prescription information.

Hypertension, angina pectoris.

Hypersensitivity. Severe left ventricular dysfunction, hypotension, marked bradycardia (less than 50 beats/minute), or cardiogenic shock, sick sinus syndrome (except in patients with functional artificial ventricular pacemaker), 2nd or 3rd degree AV block, uncompensated heart failure. Combination with beta blockers is contraindicated in patients with poor ventricular function.

NOTE:
Atrial Flutter/Fibrillation with Accessory Bypass Tract: Patients with atrial flutter or fibrillation and an accessory AV pathway (e.g. WolffParkinson-White or Lown-Ganong-Levine syndromes) have developed increased antegrade conduction across the aberrant pathway bypassing the AV node, producing a very rapid ventricular response after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated. Treatment is usually D.C.-cardioversion. Cardioversion has been used safely and effectively after oral verapamil.
Heart failure: Verapamil has a negative inotropic effect which, in most patients, is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. Verapamil should be avoided in patients with severe left ventricular dysfunction and in patients with any degree of ventricular dysfunction if they are receiving a β-adrenergic blocker. Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment.
Hypotension Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevated Liver Enzymes: Occasional elevations of transaminases and alkaline phosphatases have been reported. Patients receiving verapamil should have liver enzymes monitored eriodically. Use verapamil with caution in patients with severe hepatic impairment. ide and institution of appropriate therapy, depending upon the clinical ituation. ft ventricular outflow obstruction and a past history of left ventricular dysfunction. p
Atrioventricular Block: The effect of verapamil on AV conduction and the SA node may lead to asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR interval prolongation is correlated with verapamil plasma concentrations, especially during the early titration phase of therapy. However, higher degrees of AV block were infrequently (0.8%) observed. Marked first-degree block or progressive development to second- or third- degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil hydrochloride and institution of appropriate therapy, depending upon the clinical situation.
Patients with Hypertrophic Cardiomyopathy (IHSS) In a total of 120 patients referred to the National Institute of Health (USA) because of hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) a variety of serious adverse effects were observed following therapy with verapamil at doses up to 720 mg/day. Three patients died in pulmonary edema: all had severe le Ikapress, Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (over 20 mm Hg) capillary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4% and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction and only rarely was it necessary to discontinue verapamil therapy.
Others: Verapamil should be used with caution in patients with diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).
Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. Verapamil crosses the placenta and has been measured in umbilical cord blood Therefore, verapamil should be used during pregnancy only if clearly needed.
Use in Breastfeeding: Verapamil is excreted in human milk. Limited human data from oral administration has shown that the infant relative dose of verapamil is low (0.1 –1% of the mother’s oral dose) and that verapamil use may be compatible with breastfeeding. Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during lactation if it is essential for the welfare of the mother.
Treatment of Acute Cardiovascular Adverse Reactions: The frequency of cardiovascular adverse reactions which require therapy is rare and therefore, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, appropriate emergency measures should be applied immediately, e.g. intravenous administration of isoproterenol hydrochloride, levarterenol bitartrate, atropine (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), α-adrenergic agents (phenylephrine, metaraminol bitartrate or methoxamine) should be used to maintain blood pressure and isoproterenol and levarterenol should be avoided. If further support is necessary, inotropic agents (dopamine or dobutamine) may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Use in Patients with Impaired Hepatic Function: Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of verapamil to about 14 to 16 hours and therefore, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects should be carried out.
Use in Patients with Impaired Renal Function: About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data is available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdose.
Use in Patients with Attenuated (Decreased) Neuromuscular Transmission: It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne’s muscular dystrophy, and that it prolongs recovery from the neuromuscular blocking agent vecuronium. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
For full details see prescription information.

Peripheral oedema, hypotension, palpitations, nasal and chest congestion, shortness of breath, nausea, vomiting, dry mouth, diarrhea, constipation, cramps, flatulence, allergic hepatitis, dizziness, light headedness, nervousness, sleep disturbances, blurred vision, headache, flushing, weakness, equilibrium disturbances, dermatitis, rash, pruritus, urticaria, thrombocytopenia, gingival hyperplasia, muscle cramps, joint stiffness, arthralgia, impotence, fever, chills, sweating, sexual difficulties.
For full details see prescription information.

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 while inducers of CYP3A4 have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.
Potential drug interactions
Verapamil/Prazosin/Terazosin (Alpha Blockers):
Prazosin: Increase of about 40% in Cmax with no effect on half-life.
Terazosin: Increase of about 24% in AUC and 25% in Cmax. In both cases there is additive hypotensive effect.
Verapamil/Colchicine: Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). 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.
Verapamil/Flecainide: A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction. Effect on flecainide plasma clearance is minimal; no effect on verapamil clearance.
Verapamil/Quinidine: Pulmonary edema may occur in patients with hypertrophic obstructive cardiomyopathy (IHSS). Elevation of quinidine plasma level may occur. In a small number of patients with IHSS, concomitant use of verapamil and quinidine resulted in significant hypotension. Until further data are obtained, combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided. Oral quinidine clearance decreases by about 35%.
Verapamil/Theophylline: Concomitant use of verapamil in patients receiving theophylline has resulted in decreased oral and systemic clearance of theophylline by about 20% , elevated serum theophylline concentrations, and a prolonged serum halflife of the bronchodilator. In smokers, the reduction in theophylline clearance was lessened (about 11%). Patients receiving theophylline should be closely monitored for signs of theophylline toxicity when verapamil is administered concomitantly; serum theophylline levels should be monitored and dosage of the bronchodilator reduced if indicated.
For full details see prescription information.

Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. Verapamil crosses the placenta and has been measured in umbilical cord blood Therefore, verapamil should be used during pregnancy only if clearly needed.
Use in Breastfeeding: Verapamil is excreted in human milk. Limited human data from oral administration has shown that the infant relative dose of verapamil is low (0.1 –1% of the mother’s oral dose) and that verapamil use may be compatible with breastfeeding. Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during lactation if it is essential for the welfare of the mother.

Symptoms:  Hypotension, bradycardia up to high degree AV block and sinus arrest, hyperglycemia, stupor, metabolic acidosis Fatalities have occurred as a result of overdose.
Treatment: Treatment of overdose should be supportive. β-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel, and have been used effectively in treatment of deliberate overdose with verapamil. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopagents or cardiac pacing, respectively. Asystole should be handled by the usual measures, including cardiopulmonary resuscitation.