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Can you take doxycycline safely with milk? YES or NO?!

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Can you take doxycycline safely with milk? YES or NO?!

Postby Martian » Fri 25 Dec 2009 15:13

The question is regularly asked: can you take doxycycline with milk? One could avoid this problem by taking it with water, but some people get problems with their stomach. Milk allegedly makes one tolerate the doxycycline better. But, doesn't the calcium in the milk interfere with the absorption of doxycycline?

This was asked again on the Dutch Lyme forum a few weeks ago. If you research it, you find contradicting information: from patients, from doctors, from pharmacy, perhaps even from science. I can't find a certain answer, and so would advise people to avoid taking doxycycline with milk if possible.

Check out the article below, about a court verdict related to doxycycline taken with milk. (WTF!)

Source: http://litigationcenter.bna.com/pic2/li ... enDocument
Pharmacy Created Express Warranty Through Information Pamphlet, Court Says

A pharmacy's information pamphlet expressly warranted that the antibiotic doxycycline could be taken safely with milk, even though calcium lowers the drug's absorption rate, a Maryland appeals court held June 3 (Rite Aid Corp. v. Levy-Gray, Md. Ct. Spec. App., No. 0133, September Term 2004, 6/3/05).

The Maryland Court of Special Appeals upheld a $250,000 verdict to a woman who developed complications of Lyme disease because her diet, high in dairy products, interfered with the effectiveness of the doxycycline.

The court also said the plaintiff presented reliable expert medical testimony addressing the causal link between her diet, the compromised treatment, and her condition.

Ellen Levy-Gray consulted her physician in October 2000 after suffering pain and fever for a week. Dr. Christine Bell-Lafferman referred Levy-Gray to Dr. Ronald W. Geckler, an infectious disease specialist, after blood tests were positive for Lyme Disease. Gecker confirmed the Lyme diagnosis and prescribed doxycycline, an antibiotic in the tetracycline family.

According to the opinion, Geckler did not provide Levy-Gray with any prescribing information other than dose and frequency, explaining that he relied on pharmacies to provide specific information on the characteristics of prescription medications.

Plaintiff Receives Drug Pamphlet.

Levy-Gray filled her prescription at Rite Aid Pharmacy #4465, in Timonium, Md. Along with her prescription, the plaintiff received from Rite-Aid a "patient package insert," (PPI) entitled "Rite ADVICE." The cover page of the pamphlet informed patients that "Inside is everything you need to know about your prescription. It covers everything from dosage to side effects."

Additionally, the inside of the pamphlet stated, in part, "HOW TO TAKE THIS MEDICATION: Take each dose with a full glass of water … or more. … Take with food or milk if stomach upset occurs unless your doctor directs you otherwise. Avoid taking antacids containing magnesium, aluminum, or calcium, sucralfate, iron preparations or vitamin (zinc) products within 2-3 hours of taking this medication. These products bind with the medicine preventing its absorption."

Levy-Gray testified she consumed a diet high in dairy products because she was nursing a baby and because she was experiencing an upset stomach from the medication. Her Lyme symptoms did not improve with treatment, and in November 2000, she spoke with her brother, a urological oncologist in Seattle, Wash. Dr. David Levy told her that the calcium in dairy products impedes the absorption of the antibiotic.

According to the opinion, Levy-Gray returned to Bell-Lafferman, told her about the milk issue, and received a prescription refill. The plaintiff's condition began to improve several days after she stopped using milk products. However, Levy-Gray's condition never fully returned to normal. She consulted with Dr. Charles A. Haile, a specialist who treats 30 to 40 Lyme disease patients each year. Haile determined that Levy-Gray was suffering from post-Lyme syndrome, a chronic autoimmune response in which patients experience symptoms that can mimic Lyme disease even in the absence of active infection.

Plaintiff Sues Rite Aid.

Levy-Gray sued Rite Aid. She asserted that her ingestion of dairy products reduced the absorption of the doxycycline, preventing it from operating as effectively as it otherwise would have and proximately causing her post-Lyme syndrome. The trial court permitted the case to go to the jury on two theories, negligence and breach of express warranty. The jury found for Levy-Gray on the warranty claim and found for Rite-Aid on the negligence claim. Cross-appeals were filed.

Rite Aid argued the law does not recognize a cause of action against pharmacists for breach of express warranty, and contended the Rite Aid patient brochure made no promise concerning the performance of doxycycline and was not part of the basis of the bargain between the parties.

Rite Aid's argument is an offshoot of the learned intermediary principle, which holds that a drug manufacturer has a duty to warn physicians about the health effects of prescription medications. Because patients rely on physicians to impart health information regarding prescription drugs, there can be no express warranty from a pharmacist, Rite Aid argued.

Doctor, Patient Both Rely on Pharmacy.

But in this case, the court said, "We cannot hold as a matter of law that Ms. Levy-Gray relied solely on Dr. Geckler to describe for her the characteristics of doxycycline, because he did not advise her of the drug's characteristics or how it should be taken. Rather, Dr. Geckler relied on the dispensing pharmacist to furnish that information to the patient and, perforce, plaintiff also relied on the dispensing pharmacist."

Indeed, the court said, "The PPI furnished to Ms. Levy-Gray invited her reliance and evidences Rite Aid's intent that she rely on the affirmations of fact about doxycycline contained in the PPI."

Whether the Rite ADVICE pamphlet contains an express warranty under Maryland CL Section 2-313 is a much closer question on which there is a dearth of authority, the court said. The statute requires "an affirmative statement of fact by the seller about the goods."

Rite Aid, drawing on cases in which manufacturers were claimed to have made an express warranty, contended that "there must be a promise concerning the performance or safety of the drug involved."

Representation of Drug's Compatibility With Milk.

In this case, the express warranty rests on the statement: "Take [doxycycline] with food or milk if stomach upset occurs unless your doctor directs you otherwise." This statement, the court said, is sufficient for a jury reasonably to conclude that Rite Aid represented to the plaintiff that a characteristic or quality of doxycycline was that it was compatible with food or milk.

But the closest the Rite ADVICE pamphlet comes to the characteristic of absorption is the sentence that instructed patients to avoid taking antacids that contained calcium and several other minerals. Reasonable persons certainly could read this sentence as limited to over-the-counter or prescription antacids, including those with calcium, the court said.

It is true that the Rite ADVICE pamphlet states in bold type that "it should not be construed to indicate that use of the drug is safe, appropriate, or effective for you." But this statement must be read in the context of the Rite ADVICE pamphlet as a whole, the court said. "To hold that that general disclaimer precludes any express warranty in this case requires a judicial finding that no reasonable person could read the Rite ADVICE pamphlet without concluding that the general statement negated the more particular description of doxycycline, i.e., that it could be taken with food or milk.

"Whether the disclaimer took the statement of the compatibility characteristic of doxycycline out of the bargain was a question of fact for the jury," the opinion said.

Rite Aid also argued that an express warranty finding rests on the requirement that the affirmation of fact become part of the basis of the bargain. But the court rejected the defendant's contention that there could be no warranty because the plaintiff received the pamphlet after she purchased the drug. "It proves too much, to apply to written warranties a requirement of pre-sale knowledge by the buyer of the affirmation of fact," the court said.

Expert Causation Testimony Sufficient.

The court also said Levy-Gray's expert testimony on causation was sufficient. Dr. Neil A. Crane, board-certified in internal medicine and infectious diseases, treated two or three cases of Lyme disease annually, for which he prescribed doxycycline. He advised his patients "to avoid food altogether, take it with water, but especially avoid calcium-containing wafers such as antacids … and dairy products that contain calcium."

Based on records from Haile and Bell-Lafferman, Crane reached the conclusion that "milk and dairy products interfered with [Plaintiff's] therapy." He explained that Levy-Gray was cured of Lyme disease, but then had post-infectious complications, which generally does not happen with proper treatment. Records also indicated she began to improve after she stopped using milk products.

Bell-Lafferman, in addition to practicing internal medicine, holds a graduate degree in clinical pharmacology, the court said. She sees some five Lyme disease patients a month. Bell-Lafferman agreed that patients taking doxycycline should avoid dairy products. Based on general knowledge of the tetracycline family of antibiotics and on Levy-Gray's course of treatment, Bell-Lafferman agreed that the plaintiff's post-Lyme disease symptoms resulted from decreased absorption caused by the ingestion of milk products.

Bell-Lafferman explained, "Temporally that shows me medically that she had a decreased effect of the drug before she stopped taking it with milk. We frequently judge efficacy of those kinds of things."

Crane's and Bell-Lafferman's testimony rested on a sufficiently sound basis to be admissible, the court concluded.

The court also rejected Rite-Aid's preemption argument, citing many decisions holding that FDA approval of a prescription drug does not preempt claims against the manufacturer. It is only logical that "approval does not preempt state law claims based on a PPI which a pharmacy, unregulated by the FDA, chooses to cause to be produced and to distribute to customers at the point of sale," the opinion said.

Because of its ruling in the plaintiff's favor on Rite-Aid's cross-appeal, the court did not rule on her cross-appeal.

Retired Judge Lawrence F. Rodowsky wrote the opinion.

Craig Franco of Odin, Feldman & Pittleman in Fairfax, Va., represented Levy-Gray.

Eric Lasker of Spriggs & Hollingsworth in Washington, D.C., represented Rite Aid.
Martian
 
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Re: Can you take doxycycline safely with milk? YES or NO?!

Postby rlstanley » Fri 25 Dec 2009 23:22

http://www.medscape.com/druginfo/monogr ... ph&secid=3


Monograph - Doxycycline Calcium, Doxycycline Hyclate, Doxycycline Monohydrate

Pharmacokinetics



•Absorption

Approximately 90–100% of an oral dose of doxycycline hyclate is absorbed from the GI tract in fasting adults. Absorption takes place principally in the stomach and upper small intestine. Commercially available doxycycline hyclate extended-release tablets contain coated doxycycline hyclate pellets with a pH-dependent coating designed to delay release of the drug until the pellets reach the higher pH environment of the small intestine.

Following oral administration of capsules containing doxycycline hyclate in fasting adults with normal renal function, peak serum concentrations of doxycycline are attained within 1.5–4 hours and average 1.5–2.1 mcg/mL following a single 100-mg dose and 2.6–3 mcg/mL following a single 200-mg dose.

Following oral administration of a single 200-mg dose of doxycycline monohydrate in healthy adults, peak serum concentrations of doxycycline are attained within approximately 2.5 hours and average about 3.6 mcg/mL.

In healthy fasting adults, mean peak serum concentrations of 1.1 mcg/mL are attained at a mean of 2.6 hours after a single 100-mg dose of doxycycline as extended-release tablets containing doxycycline hyclate pellets.

Following IV infusion over 1 hour of 100 mg of doxycycline as the hyclate (in a concentration of 0.4 mg/mL), peak serum concentrations of the drug average 2.5 mcg/mL. Following IV infusion over 2 hours of 200 mg of doxycycline as the hyclate (in a concentration of 0.4 mg/mL), peak serum concentrations of the drug average 3.6 mcg/mL.

Excessive accumulation of doxycycline does not appear to occur when usually recommended dosages of the drug are used in patients with normal or impairment renal function.

Because tetracyclines readily chelate divalent or trivalent cations including aluminum, calcium, iron, and magnesium, concurrent oral administration of antacids and other drugs containing these cations may decrease oral absorption of doxycycline preparations. Of the currently available tetracyclines, doxycycline has the least affinity for calcium ions. (See Drug Interactions in the Tetracyclines General Statement 8:12.24.)

Effect of Food or Milk

The effect of food or milk on GI absorption of doxycycline appears to be variable, and further study is needed to clarify whether this variability depends on the specific salt (doxycycline calcium, doxycycline hyclate, doxycycline monohydrate) or dosage form (conventional capsules, tablets, or oral suspension; extended-release capsules or tablets) and/or the food parameters (food with or without milk, high- or low-fat meal, whole or skim milk). There is evidence that administration with food or milk can decrease the rate and extent of absorption of oral doxycycline; however, a slight increase in the extent of absorption also has been reported in some individuals who received the drug with food. Although a few manufacturers and clinicians suggest that the effect of simultaneous ingestion of food or milk is not likely to be clinically important and doxycycline may be administered with food or milk, other manufacturers state the clinical importance of this effect is unclear, and some clinicians suggest that doxycycline, like some other tetracyclines, should not be administered with milk.

In one study evaluating doxycycline (unspecified preparation) in a limited number of healthy adults, concomitant administration of the drug with food increased the time to peak serum concentrations from 2 hours to 4 hours, but did not reduce peak serum doxycycline concentrations. In a study using doxycycline hyclate conventional capsules (Vibramycin®) in a limited number of healthy adults, concomitant administration of a single 200-mg dose of doxycycline with a high-fat or high-protein meal decreased serum doxycycline concentrations by approximately 20% compared with administration in the fasting state.

In a cross-over study in healthy adult males, concomitant administration of a single 100-mg dose of doxycycline as an extended-release tablet containing doxycycline hyclate pellets (Doryx®) with a high-fat, high-calorie meal resulted in a 24% decrease in mean peak serum doxycycline concentrations and a 13% decrease in the mean area under the plasma concentration-time curve (AUC) of the drug compared with administration in the fasting state. Although mean peak serum concentrations were 1.1 mcg/mL when the dose was given in the fasting state, mean peak serum concentrations were 0.87 mcg/mL when the dose was given with a high-fat, high-calorie meal. The clinical importance of this effect is unclear.

Studies evaluating the effect of concomitant administration of doxycycline and milk have given inconsistent results. In an early study evaluating doxycycline (unspecified preparation) in a limited number of healthy adults, administration with milk (without food) reduced the peak serum concentration by about 20%, but did not affect the time to peak concentrations. In a study evaluating single 200-mg doses of doxycycline as doxycycline hyclate conventional capsules (Vibramycin®), there was no difference in mean serum doxycycline concentrations attained (over the first 24 hours after the dose) when the dose was given with either 150 mL of milk or water. Conversely, in another study in healthy adults, peak serum concentrations were 24% lower and the AUC was 30–35% lower when a 200-mg dose of doxycycline (soft gelatin capsules) was given with 300 mL of milk compared with administration with the same amount of water. In a study using single 100-mg doses of doxycycline conventional capsules containing the monohydrate (Vibramycin®), absorption of the drug was only slightly impaired by ingestion with a glass of skim milk (peak serum concentrations 1.45 mcg/mL) compared with administration in the fasting state (peak serum concentrations 1.79 mcg/mL). However, when administered with both food and milk, peak serum doxycycline concentrations were only 1.18 mcg/mL and were not attained until 4 hours after the dose.

The effect of food and milk on GI absorption of doxycycline is less than that reported with some other tetracyclines (e.g., demeclocycline, tetracycline hydrochloride). It has been suggested that milk may have a lesser effect on GI absorption of doxycycline because the drug has higher lipophilicity and a lower affinity for calcium than these other tetracycline derivatives.


•Elimination

The serum half-life of doxycycline is about 15–16 hours after a single dose and about 22 hours after multiple doses in patients with normal renal function. In patients with severe renal impairment, the serum half-life of doxycycline is reported to be 18–26 hours after a single dose, and 20–30 hours after multiple doses. The serum half-life of doxycycline is not altered in patients undergoing hemodialysis.

In patients with normal renal function, approximately 20–26% of a single oral or IV dose of doxycycline is excreted in urine and 20–40% is excreted in feces within 48 hours as active drug. In patients with creatinine clearances less than 10 mL/minute, the fraction of doxycycline excreted in urine within 72 hours may decrease to about 1–5%. Although it was previously suggested that doxycycline is partially metabolized in the liver, the drug does not appear to be metabolized but is partially deactivated in the intestine by chelate formation.


--------------------------------------------------------------------------------

AHFS Drug Information. (CR) Copyright, 1959-2009, Selected Revisions January 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


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