Ciplar

A widely used non-cardioselective beta-adrenergic antagonist. R,S-Ciplar is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety.

Hypertension

Ciplar tablets USP are indicated in the management of hypertension. It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic. Ciplar tablets USP are not indicated in the management of hypertensive emergencies.

Angina Pectoris Due to Coronary Atherosclerosis

Ciplar tablets USP are indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Atrial Fibrillation

Ciplar tablets USP are indicated to control ventricular rate in patients with atrial fibrillation and a rapid ventricular response.

Myocardial Infarction

Ciplar tablets USP are indicated to reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Migraine

Ciplar tablets USP are indicated for the prophylaxis of common migraine headache. The efficacy of Ciplar in the treatment of a migraine attack that has started has not been established, and Ciplar is not indicated for such use.

Essential Tremor

Ciplar tablets USP are indicated in the management of familial or hereditary essential tremor. Familial or essential tremor consists of involuntary, rhythmic, oscillatory movements, usually limited to the upper limbs. It is absent at rest, but occurs when the limb is held in a fixed posture or position against gravity and during active movement. Ciplar tablets USP cause a reduction in the tremor amplitude, but not in the tremor frequency. Ciplar tablets USP are not indicated for the treatment of tremor associated with Parkinsonism.

Hypertrophic Subaortic Stenosis

Ciplar tablets USP improve NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.

Pheochromocytoma

Ciplar tablets USP are indicated as an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Ciplar is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure may reduce the risk of stroke and heart attacks.

Ciplar is also used to treat severe chest pain (angina), migraine headaches, or hypertrophic subaortic stenosis (thickened heart muscle).

Ciplar may also be used to treat irregular heartbeats, tremors, or pheochromocytoma (adrenal gland tumor). It may also be used to reduce the risk of death in patients who have heart attacks.

Ciplar oral solution is used to treat proliferating infantile hemangioma.

Ciplar is a beta-blocker. It works by affecting the response to nerve impulses in certain parts of the body, like the heart. As a result, the heart beats slower and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

Ciplar is available only with your doctor's prescription.

General

Ciplar extended-release capsules provide Ciplar in a sustained-release capsule for administration once daily. If patients are switched from Ciplar tablets to Ciplar extended-release capsules, care should be taken to assure that the desired therapeutic effect is maintained. Ciplar extended-release capsules should not be considered a simple mg-for-mg substitute for Ciplar tablets. Ciplar extended-release capsules have different kinetics and produce lower blood levels. Retitration may be necessary, especially to maintain effectiveness at the end of the 24-hour dosing interval.

Hypertension

The usual initial dosage is 80 mg Ciplar extended-release capsules once daily, whether used alone or added to a diuretic. The dosage may be increased to 120 mg once daily or higher until adequate blood pressure control is achieved. The usual maintenance dosage is 120 to 160 mg once daily. In some instances a dosage of 640 mg may be required. The time needed for full hypertensive response to a given dosage is variable and may range from a few days to several weeks.

Angina Pectoris

Starting with 80 mg Ciplar extended-release capsules once daily, dosage should be gradually increased at three- to seven-day intervals until optimal response is obtained. Although individual patients may respond at any dosage level, the average optimal dosage appears to be 160 mg once daily. In angina pectoris, the value and safety of dosage exceeding 320 mg per day have not been established.

If treatment is to be discontinued, reduce dosage gradually over a period of a few weeks.

Migraine

The initial oral dose is 80 mg Ciplar extended-release capsules once daily. The usual effective dose range is 160 to 240 mg once daily. The dosage may be increased gradually to achieve optimal migraine prophylaxis. If a satisfactory response is not obtained within four to six weeks after reaching the maximal dose, Ciplar extended-release capsules therapy should be discontinued. It may be advisable to withdraw the drug gradually over a period of several weeks depending on the patient's age, comorbidity, and dose of Ciplar extended-release capsules.

Hypertrophic Subaortic Stenosis

The usual dosage is 80 to 160 mg Ciplar extended-release capsules once daily.

See also:
What is the most important information I should know about Ciplar?

Ciplar must not be used if there is a history of bronchial asthma or bronchospasm.

Bronchospasm can usually be reversed by beta-2 agonist bronchodilators such as salbutamol. Large doses of the beta-2-agonist bronchodilator may be required to overcome the beta-blockade produced by Ciplar and the dose should be titrated according to the clinical response; both intravenous and inhalational administration should be considered. The use of intravenous aminophylline and/or the use of ipratropium, (given by nebuliser), may also be considered. Glucagon (1 to 2 mg given intravenously) has also been reported to produce a bronchodilator effect in asthmatic patients. Oxygen or artificial ventilation may be required in severe cases.

Ciplar as with other beta-blockers must not be used in patients with any of the following: Known hypersensitivity to the substance; bradycardia; cardiogenic shock; hypotension; metabolic acidosis; after prolonged fasting; severe peripheral arterial circulatory disturbances; second or third degree heart block; sick sinus syndrome; untreated (with an alpha adrenoceptor antagonist) phaeochromocytoma; uncontrolled heart failure; Prinzmetal's angina.

Ciplar must not be used in patients prone to hypoglycaemia, i.e., patients after prolonged fasting or patients with restricted counter-regulatory reserves. Patients with restricted-counter regulatory reserves may have reduced autonomic and hormonal responses to hypoglycaemia which includes glycogenolysis, gluconeogenesis and/or impaired modulation of insulin secretion. Patients at risk for an inadequate response to hypoglycaemia includes individuals with malnutrition, prolonged fasting, starvation, chronic liver disease, diabetes and concomitant use of drugs which block the full response to catecholamines.

Use Ciplar solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Ciplar solution comes with extra patient information sheets called a Medication Guide and Instructions for Use. Read them carefully. Read them again each time you get Ciplar solution refilled.
• Do NOT shake Ciplar solution before use.
• Use the syringe that comes with Ciplar solution to measure the dose. Ask the pharmacist for help if you are unsure of how to measure the dose.
• Give Ciplar solution right into your child's mouth. If needed, Ciplar solution may be mixed in a small amount of milk or fruit juice and given in a baby's bottle.
• Give Ciplar solution with or right after a feeding.
• Give doses of Ciplar solution at least 9 hours apart.
• The dose of Ciplar solution may need to be changed as your child's weight changes. Have your child's weight checked often. Talk with the doctor before changing your child's dose.
• Give Ciplar solution on a regular schedule to get the most benefit from it. Giving Ciplar solution at the same time each day will help you remember to give it.
• If your child spits up a dose or if you are not sure your child got all of the medicine, do not give another dose. Wait until the next scheduled dose.
• If you miss giving your child a dose of Ciplar solution, give it as soon as possible. If it is almost time for the next dose, skip giving the missed dose and go back to your child's regular dosing schedule. Do not give 2 doses at once.

Ask your health care provider any questions you may have about how to use Ciplar solution.

Use: Labeled Indications

Angina, chronic stable: To decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Cardiac arrhythmias: Control of supraventricular arrhythmias (eg, atrial fibrillation and flutter, atrioventricular nodal reentrant tachycardia) and ventricular tachycardias (eg, catecholamine-induced arrhythmias, digoxin toxicity).

Essential tremor: Management of familial or hereditary essential tremor.

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).

Migraine headache prophylaxis: Prophylaxis of common migraine headache.

Myocardial infarction, early treatment and secondary prevention: To reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Obstructive hypertrophic cardiomyopathy: Symptomatic treatment of obstructive hypertrophic cardiomyopathy (formerly known as hypertrophic subaortic stenosis).

Pheochromocytoma: As an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Proliferating infantile hemangioma (Ciplar): Treatment of proliferating infantile hemangioma requiring systemic therapy.

Off Label Uses

Akathisia, antipsychotic-induced

Data from a limited number of patients in 5 randomized, double-blind, controlled studies support the use of Ciplar in antipsychotic-induced akathisia.

Based on the American Association for the Study of Liver Diseases guidelines on the management of portal hypertensive bleeding in cirrhosis and the British Society of Gastroenterology guidelines on the management of variceal hemorrhage in cirrhotic patients, use of nonselective beta-blockers, such as Ciplar, is effective and recommended for primary and secondary prophylaxis of variceal hemorrhage.

See also:
What other drugs will affect Ciplar?

Ciplar hvdrochloride (Ciplar® (Ciplar) )

Patients receiving catecholamine-depleting drugs such as reserpine should be closely observed if Inderide is administered. The added catecholamine-blocking action may produce an excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Caution should be exercised when patients receiving a beta blocker are administered a calcium-channel blocking drug, especially intravenous verapamil, for both agents may depress myocardial contractility or atrioventricular conduction. On rare occasions, the concomitant intravenous use of a beta blocker and verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.

Hypotension and cardiac arrest have been reported with the concomitant use of Ciplar and haloperidol.

Aluminum hydroxide gel greatly reduces intestinal absorption of Ciplar.

Alcohol, when used concomitantly with Ciplar, may increase plasma levels of Ciplar.

Phenytoin, phenobarbitone, and rifampin accelerate Ciplar clearance.

Chlorpromazine, when used concomitantly with Ciplar, results in increased plasma levels of both drugs.

Antipyrine and lidocaine have reduced clearance when used concomitantly with Ciplar.

Thyroxine may result in a lower than expected TS concentration when used concomitantly with Ciplar.

Cimetidine decreases the hepatic metabolism of Ciplar, delaying elimination and increasing blood levels.

Theophylline clearance is reduced when used concomitantly with Ciplar.

Hydrochlorothiazide

Thiazide drugs may increase the responsiveness to tubocurarine.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Hypokalemia may develop during concomitant use of corticosteroids or ACTH.

Drug/Laboratory Test Interactions

Hydrochlorothiazide

Thiazides may decrease serum FBI levels without signs of thyroid disturbance.

Thiazides should be discontinued before carrying out tests for parathyroid function.

See also:
What are the possible side effects of Ciplar?

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Hypoglycemia and related events, like hypoglycemic seizure.
• Bronchospasm.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in clinical practice.

Clinical Trials Experience with Ciplar in Infants with proliferating infantile hemangioma

In clinical trials for proliferating infantile hemangioma, the most frequently reported adverse reactions ( > 10%) in infants treated with Ciplar were sleep disorders, aggravated respiratory tract infections such as bronchitis and bronchiolitis associated with cough and fever, diarrhea, and vomiting. Adverse reactions led to treatment discontinuation in fewer than 2% of treated patients.

Overall, 479 patients in the pooled safety population were exposed to study drug in the clinical study program (456 in placebo-controlled trials). A total of 424 patients were treated with Ciplar at doses 1.2 mg/kg/day or 3.4 mg/kg/day for 3 or 6 months. Of these, 63% of patients were aged 91-150 days and 37% were aged 35-90 days at randomization.

The following table lists according to the dosage the most common adverse reactions (treatment-emergent adverse events with an incidence at least 3% greater on one of the two doses than on placebo).

Table 2: Treatment-emergent adverse events occurring at least 3% more often on Ciplar than on placebo.

The following adverse events have been observed during clinical studies, with an incidence of less than 1%:

Cardiac disorders: Second degree atrioventricular heart block, in a patient with underlying conduction disorder, required definitive treatment discontinuation.

Skin and subcutaneous tissue disorders: Urticaria, alopecia

Investigations: Decreased blood glucose, decreased heart rate

Compassionate Use Program

More than 600 infants received Ciplar in a compassionate use program (CUP). Mean age at treatment initiation was 3.6 months. Mean dose of Ciplar was 2.2 mg/kg/day and mean treatment duration was 7.1 months.

The adverse reactions reported in the CUP were similar to the ADRs observed during clinical trials but some were more severe.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Ciplar. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These adverse reactions are as follows:

Blood and lymphatic system disorders: Agranulocytosis

Psychiatric disorders: Hallucination

Skin and subcutaneous tissues disorders: Purpura