generic times: product profiles

APRIL 01, 2007
Jim Middleton, BS, RPh

Metoprolol Extended-release Tablets

The hazards of misinterpreting sound-alike and look-alike drugs are becoming an increasing concern among clinicians. In 2005, the FDA distributed a letter warning about medication errors involving the beta-blocker metoprolol, whose brand name Toprol was being confused with Topamax and Tegretol on some hospital orders and outpatient prescriptions. The letter suggested using both brand and generic names when ordering this trio of medications.

Metoprolol, indicated for the treatment of hypertension, angina, and heart failure, has recently become available as a generic in its extended-release version. Current generic sources for metoprolol extended-release tablets are limited to the 25-mg strength, available from Par Pharmaceutical Companies Inc and Sandoz.


Unlike some beta-blocking drugs, metoprolol demonstrates selective inhibition of beta1 adrenergic receptors at low doses. Only at higher doses does beta2 inhibition occur.

The exact mechanism of effect of beta-blockers has not been fully determined. Some studies suggest a decrease in sympathetic outflow from the central nervous system; others note a suppression of renin release. At the cardiac level, the reduction of heart rate and blocking of catecholaminebased activity is thought to explain its effectiveness for angina.

Dosage and Administration

Metoprolol is available in extended-release formulations to enhance convenience and patient adherence. For hypertension, the extended-release dose begins with a daily dose of 25 to 100 mg, with a 400-mg daily maximum. For angina, polymorphic ventricular tachycardia, and prophylaxis of heart attack, the initial daily dose is 100 mg, with the same 400-mg daily limit. Elderly patients should initiate treatment with 25 to 50 mg daily as a single dose, with increases at 1-to 2-week intervals.

Unlike many extended-release formulations, scored metoprolol can be divided into half tablets with a constant drug delivery over 24 hours. Nevertheless, the whole or half tablets should not be further chewed or crushed.

Safety Profile

Metoprolol should be avoided in the presence of sick sinus syndrome or sinus-mediated bradycardia, in severe peripheral artery disease, and during the final 2 trimesters of pregnancy. Beta blockade presents a challenge with concurrent bronchial disease states, such as asthma. Metoprolol has greater beta1 specificity, however, and with careful monitoring can be employed with coexisting bronchospastic disorders.

Patients with diabetes may experience additive hypoglycemic effects with beta-blockers; metoprolol appears to be well-tolerated among this patient population. The use of calcium channel blockers such as verapamil or diltiazem, however, may still potentiate bradycardia or induce heart block.

Other drug interactions include enhanced vertigo with alpha-blocking drugs such as prazosin or terazosin; bradycardia and hypotension may be amplified with concurrent use of selective serotonin reuptake inhibitors and phenothiazines, or drugs that inhibit the CYP2D6 metabolic enzyme.

Several naturopathic treatments may also affect metoprolol activity by their action on the body's vasopressor response. Gotu kola, licorice, and ephedra may interfere with the hypotensive effects of metoprolol, while hawthorn and quinine may enhance the blood pressure-lowering effects in unpredictable ways.

When beta-blocker therapy is to be withdrawn, it should be done slowly to avoid rebound tachycardia, hypertension, or cardiac ischemia.

Clinical Outlook

Metoprolol extended-release tablets offer a more effective means of maintaining uniform plasma levels and therapeutic response than their immediate- release relatives. At a single daily dose, they offer a convenient opportunity to promote adherence, especially among patients receiving therapy involving multiple drugs.

Pilocarpine Oral Tablets

Sjögren's syndrome is a disease that crosses all populations, locations, and age groups. Women are more prone to the condition, with the average age for peak symptoms occurring between ages 40 and 60 years. The salivary glands are infiltrated by lymphocytes, decreasing parotid flow of saliva. The main symptom of xerostomia may be combined with dry eyes and can also be a consequence of connective tissue diseases such as rheumatoid arthritis or lupus.

Treatment of Sjögren's syndrome is directed at the xerostomia, with cholinergic stimulation being considered a most effective therapy. Pilocarpine is a classic cholinergic agent useful for this condition, now available generically in 2 strengths. The 5-mg tablets are available from Sandoz, Actavis, Roxane Laboratories, and Lannett Co Inc. The 7.5-mg tablets are manufactured by Actavis.


A classic stimulator of the salivationlacrimation- urination-defecation response, pilocarpine is a cholinergic drug that acts upon muscarinic receptors.

Dosing and Administration

In addition to Sjögren's syndrome, pilocarpine tablets are useful in treating xerostomia resulting from cancer radiation therapy to the neck and head.

Dosing for Sjögren's syndrome is generally 5 mg, taken up to 4 times daily. For xerostomia secondary to cancer therapy, the dose generally begins at 5 mg 3 times daily, with titration up to 10 mg 3 times daily. Most patients require a total daily dose of 20 mg. Single doses above 10 mg and total daily doses above 30 mg are not recommended. The dosing should be continued for a minimum of 90 days to obtain maximum effectiveness.

Whereas taking pilocarpine tablets after eating helps reduce some of its untoward gastrointestinal effects, highfat meals will diminish its effective rate of absorption.

Safety Profile

Pilocarpine tablets are contraindicated for patients with poorly controlled asthma, glaucoma, or severe hepatic impairment. Caution is also necessary with the presence of gallstones, nephrolithiasis, or biliary tract disease. The cholinergic nature of pilocarpine brings gastrointestinal effects of diarrhea, nausea, vomiting, and excessive salivation. Sweating is also likely.

The use of oral pilocarpine is not recommended for patients under the age of 6 years. Atropine is the favored antidote in the case of overdose, with epinephrine employed to treat possible respiratory or cardiovascular consequences of oral pilocarpine use.

Although oral pilocarpine may be effective in reducing xerostomia caused by antidepressants and other drugs, the FDA has not granted approval for that indication due to lack of specific clinical studies.

Clinical Outlook

Sjögren's syndrome, initially counted among the registry of rare disorders, is now considered the second most common autoimmune rheumatic disease, with an incidence in nearly 3 million people in the United States alone. It also represents a major health problem among women that is regarded as underdiagnosed or treated. Fortunately, symptomatic treatment is available with the generic versions of pilocarpine tablets.

Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.