Lansoprazole (Prevacid): Drug Whys
Generic Name: Lansoprazole (no generic available — U.S. patent expires May 2009)
Common Brand Name: Prevacid (TAP Pharmaceuticals — U.S.)
Popularity: 21st most commonly prescribed drug between 2002 — 2007 (U.S.)
Class: PPI (proton pump inhibitor)
Treatment Uses — For treatment of active duodenal ulcer and maintenance treatment of healed duodenal ulcers. Treatment of GERD (gastroesophageal reflux disease) with heartburn symptoms, all grades of erosive esophagitis as well as maintenance treatment of healed esophageal erosions. Treatment of gastric ulcers. Used as part of a multidrug regimen for H. pylori eradication to reduce risk of duodenal ulcer recurrence. NSAID (non-steroidal anti-inflammatory drug) induced gastric ulcer prevention and treatment. Treatment of pathologic gastric hypersecretory conditions (such as Zollinger-Ellison syndrome). Has been used to improve pulmonary function in children with cystic fibrosis. May be used for treatment of Barrett’s esophagus.
PPIs work by blocking an enzyme that tells the stomach to produce more acid. Excessive amounts of acid produce heartburn, damage the lining of the stomach (causing ulcers), and when regurgitated back up the esophagus, result in major heartburn and can damage the lining of the esophagus. Other medications used to treat these symptoms include over-the-counter antacids and H2 blockers (a class of drugs that work to reduce stomach acid production through different mechanism than PPIs). For long term (four to eight weeks or longer) relief of pain and for healing certain ulcers, PPIs are more effective than H2 blockers. Usual PPI doses block more than 90 percent of stomach acid secretion versus 50 to 80 percent with H2 blockers. However, H2 blockers work faster (45-60 minutes) than PPIs (days), making antacids or H2 blockers the preferred treatment for sporadic heartburn or immediate symptom relief.
Dosing and Administration — For duodenal, gastric, and NSAID-associated ulcer treatment or erosive esophagitis from GERD, initial oral dosing in adults is 30 milligrams once daily. The manufacturer recommends a maintenance dose following initial treatment of these conditions in adults of 15 milligrams once daily. Recommended lengths of treatment span from four to 16 weeks, depending on the condition. Fears about long term use of PPIs come from the resulting increased circulating levels of the hormone gastrin. In rats, this has been observed to accelerate growth rates of gastrointestinal cancers. Whether the same holds true for humans is unproven. Several conditions, such as chronic heartburn from GERD, require lifelong treatment as symptoms usually return within five days of discontinuing PPI therapy. Higher doses of lansoprazole are required for hypersecretory conditions, usually starting at 60 milligrams orally each day (for adults) up to 90 milligrams twice daily. Pediatric doses for all conditions are lower than adult doses and both age and weight driven, depending on the condition being treated. Starting doses for children weighing under 30 kilograms is typically 15 milligrams daily for up to 12 weeks and 30 milligrams daily for children more than 30 kilograms. There are no published data on the safety and efficacy of lansoprazole in children less than 1 year old.
In practice, the most common use of lansoprazole is for treatment of GERD or suspected GERD. While an initial starting dose of 30 milligrams once daily is typical, continued symptoms after two weeks may require escalation to 30 milligrams twice daily dosing. Downward titration to the lowest effective dose should be the goal once symptoms are in good control. Resolution of symptoms is likely to take eight weeks or more of therapy before downward doing titrations can be attempted.
Despite manufacturer dosing recommendations for adults, actual practice varies considerably, and there is marked disagreement on both standard dosing and length of treatment. Presently, many practitioners prefer to initiate therapy at the 30 milligram daily oral dose for adults and stay at the same dosing indefinitely. While most studies to date find long-term therapy safe, there is considerable disagreement over which patients require prolonged PPI treatment.
The most common form of lansoprazole is a delayed-release capsule. It is also available as a delayed-release orally disintegrating tablet and in a packet for delayed-release oral suspension. All contain enteric-coated granules or microgranules that should not be crushed or chewed. An intravenous form of lansoprazole is available outside the United States.
Lansoprazole should be taken in the morning on an empty stomach to provide most optimal benefits. In two studies, taking lansoprazole with a meal and up to 30 minutes after eating reduced the peak levels of drug in the blood by 50 percent. Delayed-release lansoprazole capsules should be swallowed whole; the granules in the capsule should not be chewed or crushed. If unable to swallow, the capsule can be opened and the intact granules sprinkled on applesauce, pudding, cottage cheese or yogurt. The mixture should be swallowed immediately. Capsules can also be opened and mixed into 2 ounces of orange, apple, tomato, V-8, grape, pineapple or prune juice then consumed within 30 minutes.
Dose reduction of lansoprazole should be considered in patients with liver dysfunction (hepatic insufficiency) because the drug is extensively metabolized in the liver. Starting doses are recommended at 15 milligrams daily instead of the 30 milligrams daily for patients with normal liver function. Although clearance is reduced in geriatric patients, repeated daily dosing does not seem to accumulate lansoprazole; hence dosage adjustments are not necessary in the elderly.
Overdoses ranging from 320 to 900 milligrams in adults have demonstrated minimal to no clinical effects. Lansoprazole is not removed from the body by hemodialysis. On the brighter side, massive overdoses given to rats and mice did not produce deaths or any clinical signs.
Pharmacology/Pharmacokinetics/Stability — After oral administration of lasoprazole, peak concentrations appear in the bloodstream within 1.5 to 3 hours although the actual therapeutic effects of this drug do not correlate well with blood concentrations. Significant inhibition of gastric acid secretion is observed at two hours following a single dose, and becomes dramatically better with consecutive dosing. The peak response occurs between one and eight weeks, depending on the condition being treated. The duration of acid secretion inhibition is at least 24 hours after each dose and can continue for up to 40 hours after stopping maintenance therapy. The liver is responsible for nearly all lansoprazole metabolism. About one-third of lansoprazole is excreted in the urine, and two-thirds in the feces. It is not known if lansoprazole is excreted in human breast milk, but it is excreted in the breast milk of rats, suggesting that nursing mothers consider the importance of taking this medication.
Reproductive studies of lansoprazole have shown no harm to fetuses of rats or rabbits at weight based doses of up to 49 times recommended human dosing. There are no adequate, well-controlled human studies so lansoprazole should only be used during pregnancy if absolutely needed.
The mechanism of action of lansoprazole is a binding to enzymes in the digestive tract collectively known as the proton pump resulting in an inhibition of gastric acid secretion. Unlike H2 blockers, PPIs like lansoprazole do not have anticholinergic or histamine blocker properties.
Lansoprazole delayed-release capsules, oral suspension, and delayed-release orally disintegrating tablets should be stored at room temperature between 59-86 F and protected from light and moisture using a tight, light-resistant container. The most common form, delayed-release capsules, are opaque, hard gelatin, colored pink and green (15 milligrams) or pink and black (30 milligrams), with the TAP logo and “PREVACID 15” or “PREVACID 30” imprinted on the capsules.
Cautions and Warnings — Like all PPIs, lansoprazole is a relatively safe drug. Caution should be observed in the presence of liver dysfunction. The most significant and serious warning about lansoprazole applies to all PPIs: “symptomatic response does not exclude malignancy.” When symptoms appear caused by gastric acid irritation, it is not uncommon to prescribe a trial period of PPI therapy without costly, invasive tests. When PPI therapy reduces or eliminates symptoms, the positive response can lead to a conclusion that the responsible culprit is indeed GERD, a hypersecretory condition, or even an ulcer that has begun healing. Unfortunately, symptoms from esophageal and gastric cancers often respond well to PPI therapy. Hence, the warning: symptomatic response to lansoprazole does not exclude the presence of cancer.
Important Side Effects and Interactions — The most common side effects of lansoprazole are headache (2.5 to 4.7 percent of patients), diarrhea (up to 8 percent of patients, more common at doses of 60 milligrams daily), abdominal pain (1.8 percent), nausea (3.7 percent or less), and constipation (1 percent). Rarely, more serious side effects have been reported, but whether lansoprazole played a definite role in most of these cases is uncertain.
Thirty-two drugs are reported to interact with lansoprazole, none of which have good documentation. As mentioned earlier, lansoprazole should be taken on an empty stomach, preferably in the morning. Taking this drug with food significantly reduces effectiveness. Of reported food-drug interactions with lansoprazole, cranberry juice increased gastric acid so significantly that regular consumption of cranberry juice should be avoided during PPI therapy.
Average Costs — U.S.
• 15 mg /30 mg delayed release capsule (brand name Prevacid)
Patient cost: varies widely — average is $1.00 each* both strengths
Large Hospital cost: $0.25 for either strength
*( Wal Mart® and Target don’t include lansoprazole in their $4/month programs)
Consumer Reports, in conjunction with the Oregon Health & Science University Drug Effectiveness Review Project (DERP), sponsor a website called Best Buy Drugs (see references). This site provides consumers plain English reviews of scientific and evidence based literature on the effectiveness and safety of commonly prescribed drug classes. There is no evidence that any one of the five PPIs available in the United States is better than another when used at comparable doses. One PPI (omeprazole) is available over-the-counter (OTC) at an average cost of $0.79 per delayed release tablet. Compared to more than $4 per dose of lansoprazole, Consumer Reports notes that considerable savings could be available, especially for people without insurance coverage for PPIs.
1. MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed March, 2009).
2. Albany Medical Center Pharmacy, Albany, New York.
3. Consumer Reports Best Buy Drugs. The Proton Pump Inhibitors. November, 2004 update. Available online: www.CRBestBuyDrugs.org.
4. The Medical Letter. Treatment Guidelines: Drugs for Peptic Ulcers. 2 (18): 9-12, February 2004.