Sample Consults

This man calls me at the office one day after seeing a front page profile that the Griffin Daily News ran about me and my practice. He was crying and terrified that he was dying and nobody seemed to know what was wrong with him. His muscle pains and lack of control had reached the point that the Physical Therapy office had discharged him that day because he couldn’t stand up to do the exercise. His attending physician had diagnosed him with Arthritis as the problem and started NSAID therapy. After a few weeks and continuing deterioration the physician sent the patient to a Neurologist who diagnosed Perpherial Neuropathy and Arthralgia of which she prescribed three different anti-convulsant type drugs to be taken concurrently. This only made things worse and affected his sleep as well as his gait. Upon questioning the patient I learn that he had been on several Statin drugs over the past year and was presently on Crestor of which I told him to stop immediately. He informed me he had stopped a few weeks back because he had given up. I made an appointment to see him the next day even though he had not completed my normal assessment forms prior to the visit. He took the Physician’s referral letter for a Drug Therapy Consult to his attending physician for her approval and was denied. He was told that she didn’t need any help in practicing medicine. He then took it to the neurologist an was told that what could a pharmacist tell a neurologist about patient care. Anyway he came I referred him to one of my support physicians who made all the changes I recommended. Two months later I saw him for a follow-up with his wife and he had no problems walking, sitting or standing. He sort of scared me for a minute while I was talking to his wife, he drops to the floor and then pops back up and stands to show me how good he can move about. I asked him had he driven his truck any and he said he was back full time driving. I asked him did he have any leg pain while driving and he said that he did later in the day. But, his wife exclaimed that he was driving 10 and 11 hours a day. His drug bills were reduced about $800.00 a month and his wife was so impressed with his progress she scheduled an appointment for me to review her.

Patient Profile for Barry Sample Patient

________________________________________________________________________________

General Information

ID: jbt02152006

Prescriber: Doctor DoLittle M.D.

Name: Barry Sample Patient

Address: 500 Circle Dr.

City: Close by

State: GA

Zip: 30292

Country: USA

Phone: 876.234.8798

________________________________________________________________________________

Current Conditions

• hypercholesterolemia

• hypertension

• insomnia

• moderate pain

• muscle cramps

• nutritional supplementation

• osteoarthritis

• prostate cancer

• radiation therapy

• renal impairment

• sinusitis

• vertebral disc herniation

• vitiligo

________________________________________________________________________________

Current Allergies

• Codeine

________________________________________________________________________________

Current Medications

• Medication

• Aleve® Dosage: 220 mg Sig: tab 2 twice a day

• Allegra® Dosage: 180 mg Sig: tab 1 daily

• Atenolol; Chlorthalidone Dosage: 50/25 Sig: daily

• Crestor® Dosage: 20 mg Sig: daily

• Cyanocobalamin, Vitamin B12 Dosage: Drops 1mg Sig: dropperful daily

• Garlic Dosage: 400 mg Sig: daily

• Hydrocodone;Acetaminophen Dosage: 5/500mg Sig: tab 1 every 4 hr for pain

• Lunesta™ Dosage: 2 mg Sig: tab 1 or 2 at bedtime for sleep

• Nasonex® Sig: spray each nostril twice a day

• Preventive Nutrition® Coenzyme Q-10 Dosage: 60 mg Sig: tab daily

• Protopic® Sig: apply to skin as needed

• Therapeutic Multivitamin with Minerals

• Tylenol® PM Dosage: 500mg/25mg Sig: tab 2 at bedtime for sleep

________________________________________________________________________________

Dosing Parameters

Gender: Male

Birthdate: 4/13/1934

Weight: 104.09 kgs

Height: 180.34 cm

Ideal Body Weight: 74.8 kgs

Body Surface Area: 2.28 m²

Serum Creatinine: 1.5 mg/dL

Creatinine Clearance: 47.79 mL/min

________________________________________________________________________________

Notes

Title: Initial Interview & Assessment

Date: 02/15/2006

This 71 year old mentally alert white male presents a multitude of muscle and joint problems. He has muscle aches and pains to the extent that he is presently in physical therapy for treatment. A review of his drug therapy indicates serious potential problems that contribute and exacerbate these muscle conditions as well as probable cause of these problems. He stopped taking Crestor 20mg daily a month back or around the time he started PT. He is self employed owning a dump truck company and is concerned about the pain in his hip muscles he experiences when sitting for a while and then trying to stand up. Although there is no dizziness that accompanies this gait problem it seems to be all muscle related and probably due to the use of “statin” drug therapy. He is currently self-medicating with numerous neutraceuticals which I will suggest changes to later on in this report. His attending physician stopped his antihypertensive/diuretic medication this past week when he presented at her office with a blood pressure of 120/80. I do not have any average blood pressure values at this time. I gave him a Blood Pressure Log sheet to start recording his AM and PM blood pressures with pulses starting tonight and reporting back the results of these tests in about 7 days. An addendum to this report will be posted when he supplies me with his results. He complains that when he sits for a long while, which he demonstrated in my office by standing after about 45 minutes, that his ability to adjust to standing is both painful and slow. During our discussion he indicated that his hands are swollen in the mornings and require some exercise before he can open and close his fist. This may be corrected with the addition of a low dose loop diuretic. The physical therapy seems to be working and his pain is not as bad as a month or so back. He is currently taking large amounts of acetaminophen both throughout the day with Tylenol Arthritis Strength and at night with Tylenol PM. The daily amount of acetaminophen exceeds all safety parameters of 3000mg daily. His daily intake exceeds 4000mg and has to be stopped. Additionally, upon the advice of the nurse in the physician’s office he started taking 400mg of Naproxen Na. twice a day for pain. With a Creatinine Clearance of 47cc/min the continued use of this has to stop. Use of NSAID drug at this time is not a doable approach to analgesia. He had Prostate Cancer in 2001 and was treated with radiation and seems to have no problems from this procedure at this time. An assessment of the patient with the validated “Geriatric Depression Scale” shows a value of 4. This is borderline depression but treatment with the SSRI-SNRI, Effexor XR, may reduce his anxiety about his condition, improve his depression and improve his sleep habits to a degree that use of hypnotic therapy may not be necessary. Along with the use of Effexor XR for these listed reasons the effects on muscle neuropathy may also improve and hasten his return to work. Use of the Lunesta may cause some long term effects in cognition that we surely do not want to occur. Also, use of Vitamin B12, Vitamin B6 and Folic Acid should improve his lipid profile by reduction of homocystine and Methylmalonic acid levels thus reduction of lipids. Use of this combination will also improve muscle function and an overall sense of well being. A 90 day trial of Chondrotin/Glucosamine 1200/1500mg three times a day may also improve his muscle and joint pains. Supplemental analgesic therapy of Tramadol and Tylenol Extra Strength should improve his quality of life. An additional dose of Aspirin 325mg EC daily for platelet inhibition is necessary in this patient.

Title: Drug Therapy Evaluation & Recommendations

Date: 02/15/2006

Review of the drug therapy currently prescribed resulted in the following problem areas:

Aleve - Use of NSAID drug therapy in this patient for pain is contraindicated due to reductions in renal clearance CrCl of 47cc/min. Use of Tramadol & Tylenol are more geriatric friendly and can be used in place of other analgesics.

Allegra / Nasonex Spray - Although not taking these drugs presently if the need occurs due to allergy problems, daily doses are permitted.

Atenolol/chlorthalidone - use of beta blockers in the geriatric patient should be discouraged as serious problems with depression, Raynaud’s Syndrome are common place. Also other muscle pain and fatigue are results for the use of beta blockers in the geriatric. Based on a CrCl of 47cc/min use of chlorthalidone are not advised due to changes in GFR resulting in poor outcomes. Since this drug was stopped last week due to a blood pressure reading in the office of 120/80, I reserve comment as to need for blood pressure therapy until I receive the results of the Blood Pressure Log next week.

Crestor - should never been used on this patient. Based on his renal clearance use of statin therapy is not an alternative and especially this one. Crestor has more problems with Rhabodmyolysis, which is occurring in this patient, as well as liver and renal failure. Although the Creatine Kinase (CK), value of 62, is an indicator of Rhabdomyolysis, in the geriatric this value does not seem to provide warning until there is renal and hepatic damage. It is obvious that a great degree of harm has occurred form this drug being used. The physical therapy, Vitamin B therapies and time should resolve this problem and he will be able to continue his normal activities of daily living.

Lunesta, Tylenol PM - are not geriatric friendly. Use of diphenhydramine with its very high anticholinergic activity increases the patient potential for falls, confusion and many other problems. Lunesta or any crutch for sleep becomes a habit and denies the patient of good REM sleep. Use of Effexor XR should resolve these issues and improve outcomes.

Neutraceuticals - use of Garlic, Current multivitamin, CoEnzyme Q-10, B12 drops and others may have some benefits, not many if any double-blind studies have been published to substantiate any real value to their use. Multivitamin use is necessary but needs to be formulated for the geriatric patient as I will suggest later in the report.

Hydrocodone/acetaminophen - was prescribed in the past but not used at this time. This drug is not needed in this patient.

Drug Therapy Management

Stop Aleve

Stop Atenolol/Chlorthalidone

Stop Crestor

Stop B12 drops

Stop Garlic

Stop Hydrocodone/acetaminophen

Stop Lunesta (using the tapering and stopping schedule listed below)

Stop CoEnzyme Q-10

Stop Multivitamin

Stop Tylenol PM

Stop All other Tylenol products (continue use following instructions below)

New Drug Therapy

Start Vitamin B12 1000mcg IM weekly for 4 weeks then each month

Start Vitamin B6 200mg daily

Start Folic Acid 1mg daily

Start Demadex 10mg daily

Start Tramadol 50mg and Tylenol Extra Strength every 6 hours for pain as needed

Start Effexor XR 37.5mg at bedtime for 5 doses, then 37.5mg at bedtime for 5 doses then 150mg at bedtime…

Then reduce Lunesta to 2mg every other bedtime for 5 doses and discontinue

Start Centrum Silver (or like store brand) daily

Start Chondrotin / Glucosamine (CVS triple strength) tab 2 three times a day

Remember that it will take time to see all the changes that the new drug therapy will produce. After completing the titration processes that are required, we should see big improvements relating to the complaints recorded. The additional vitamin supplements should also make you feel better after 30 days or so. Antihypertensive drug therapy is questionable and we will re-evaluate this in a few weeks. Continue to keep your blood pressure and pulse log. This is very important. I feel that the B vitamin regimen will lower your Homosystine level and allow for the lipid problem to adjust itself to parameters consistent with your age. I know they will make you feel better. The Effexor XR will make you sleep better and eliminate the anxiety you are experiencing.

Let me remind you that this drug therapy regimen is thoroughly thought out and should be followed in its entirety. Choosing only bits and pieces of it may keep us from reaching our mutual goal of improvement in your quality of life and health. I am as close as your phone, so if problems occur please call me. I look forward to seeing you for a follow-up visit around the end of March or the first of May but would like a progress report weekly by phone until we have all your medication dosages adjusted for you.

________________________________________________________________________________

Drug Interactions

Naproxen (Aleve®) and Atenolol; Chlorthalidone

Severity: Moderate

NSAIDs can reduce the hypotensive effects of antihypertensives. During antihypertensive therapy with beta-blockers, high levels of vasodilatory prostaglandins are produced in response to reflex-mediated pressor mechanisms (e.g., sympathetic tone). Concurrent use of beta-blockers with NSAIDs may result in loss of antihypertensive activity due to inhibition of prostaglandin activity and decreased renin activity. NSAIDs can cause sodium and fluid retention as well as increase peripheral vascular resistance. NSAIDs can decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Concomitant administration of NSAIDs with diuretics can also increase the risk for renal insufficiency secondary to decreased renal blood flow. Patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment. Among NSAIDs, indomethacin, naproxen, and piroxicam may have the greatest pressor effect, while the effects of sulindac and nabumetone may be significantly less.

Nonsteroidal anti-inflammatory drugs (NSAIDs), to varying degrees, have been associated with an elevation in blood pressure (approximately 5 mmHg) when given over a period of weeks. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.[805] NSAIDs have been shown to attenuate the effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), vasodilators, central alpha-2 agonists, peripheral alpha-1 blockers, and angiotensin II blockers. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs.[4087] Concomitant volume depletion caused by diuretics and prostaglandin inhibition caused by naproxen may increase the risk of renal failure due to inadequate kidney perfusion. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.[3154]

Naproxen (Aleve®) and Mometasone (Nasonex®)

Severity: Moderate

Increased gastrointestinal (GI) effects are possible if naproxen is used with corticosteroids. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs.[1162] Nonsteroidal anti-inflammatory drugs should be used cautiously in patients receiving corticosteroids.

Naproxen (Aleve®) and Tacrolimus (Protopic®)

Severity: Moderate

Due to the inhibition of renal prostaglandins by naproxen, concurrent use with other nephrotoxic agents may lead to additive nephrotoxicity.[7020] Naproxen should be given with caution to patients taking aminoglycosides, amphotericin B [5062] [5068], systemic bacitracin [5062], cisplatin [5123], gold compounds [6859], ganciclovir [5173], pamidronate [7799], pentamidine [5612], tacrolimus [5342], tenofovir, PMPA [4917], foscarnet [5106], parenteral vancomycin [5198], or zoledronic acid [6318]. Monitor renal function carefully during concurrent therapy.

Tacrolimus, in the absence of overt renal impairment, may adversely affect renal function. Care should be taken in using tacrolimus with other nephrotoxic drugs.[5342] Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced (see Dosage). Patients with reduced renal function may have significant impairment of pemetrexed elimination, as most of the drug is eliminated unchanged in the urine. Pemetrexed should not be used in patients with a creatinine clearance less than 45 ml/minute.[5105] Other examples of drugs that can adversely affect renal function include acyclovir, adefovir, amphotericin B [5342], angiotensin-converting enzyme inhibitors (ACE inhibitors), systemic aminoglycosides [5342], carboplatin, cisplatin [5342], foscarnet [5118], ganciclovir [5342], nonsteroidal antiinflammatory drugs (NSAIDs) [5118], salicylates, bismuth subsalicylate, systemic bacitracin, pamidronate [7799], polymyxin B, IV pentamidine [5118] parenteral vancomycin [5118], and zoledronic acid [6318].

Naproxen (Aleve®) and Garlic, Allium sativum (Garlic)

Severity: Moderate

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen decrease platelet aggregation. Garlic, Allium sativum, ginger, Zingiber officinale, and ginkgo, Ginkgo biloba, also have clinically significant effects on platelet aggregation; concurrent use with a NSAID may lead to a potential increased risk of bleeding.[1900] [2233] [6708] A case of fatal intracerebral bleeding has been reported with the combination of ginkgo and ibuprofen.[5211]

Garlic, Allium sativum may produce clinically-significant antiplatelet effects [2233]; until more data are available, garlic should be used cautiously in patients receiving drugs with a potential risk for bleeding such as diflunisal, NSAIDs, anticoagulants, platelet inhibitors like aspirin, ASA, or thrombolytic agents. In regard to warfarin, no substantial clinical data are available to support or deny a potential for interaction; the data are limited to a random case report.[5200] A case of spontaneous spinal epidural hematoma, attributed to dysfunctional platelets from excessive garlic use in a patient not receiving concomitant anticoagulation, has been reported.[2245] Patients who choose to consume garlic supplements while receiving the listed medications should be observed clinically for evidence of adverse effects.

Atenolol; Chlorthalidone and Vitamin A (found in Therapeutic Multivitamin with Minerals)

Severity: Moderate

Thiazide diuretics may cause photosensitivity [7476] and may increase the photosensitization effects of drugs like griseofulvin, phenothiazines, retinoids [5254], sulfonamides, sulfonylureas, tetracyclines, or photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.[7476]

Atenolol; Chlorthalidone and Mometasone (Nasonex®)

Severity: Moderate

Additive hypokalemia may occur when non-potassium sparing diuretics (loop diuretics or thiazide diuretics) are coadministered with other drugs with a significant risk of hypokalemia (e.g., amphotericin B, cisplatin, corticosteroids, corticotropin, ACTH).

Atenolol; Chlorthalidone and Calcium Salts (found in Therapeutic Multivitamin with Minerals)

Severity: Moderate

Aluminum hydroxide antacids have been reported to decrease the AUC of atenolol by 57%, whereas calcium salts (lactate, gluconate, and carbonate salts) have been reported to reduce the AUC of atenolol by 32%.[4384] Twelve hours after concurrent calcium and atenolol administration, inhibition of exercise-induced tachycardia is greater compared to atenolol alone. In another study, antacids has been shown to reduce the AUC of atenolol by 33%.[4382] Separate doses of atenolol and antacids or calcium salts by at least 2 hours to minimize this potential interaction.

Prolonged use of calcium salts with thiazide diuretics can lead to the milk-alkali syndrome.[4689] Exogenous calcium and thiazide diuretics each can cause hypercalcemia, and thiazide diuretics may cause metabolic alkalosis. These are pharmacodynamic interactions. While the use of a thiazide diuretic does not preclude administration of calcium salts, these two agents should not be administered together for prolonged periods without monitoring serum calcium and other serum electrolytes.

Rosuvastatin (Crestor®) and Niacin, Niacinamide (found in Therapeutic Multivitamin with Minerals)

Severity: Moderate

HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Combination therapy with HMG-CoA reductase inhibitors and lipid-lowering doses of niacin (i.e., vitamin B3 as nicotinic acid) has been associated with myopathy and rhabdomyolysis.[4705] The manufacturer recommends that the benefit of combined use of rosuvastatin with niacin should be carefully weighed against the potential risks.[4705] During concurrent therapy, monitor for signs and symptoms of myopathy as well as periodic CK measurements.

Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (i.e., 'statins') concurrently.[5506] Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Since compounds in went yeast, Monascus purpureus are pharmacologically similar to the HMG-CoA reductase inhibitors,[5911] clinicians and patients should use this dietary supplement cautiously in combination with niacin, particularly in non-prescription use.

Acetaminophen; Hydrocodone (Hydrocodone;Acetaminophen) and Diphenhydramine (found in Tylenol® PM)

Severity: Moderate

Concomitant use of hydrocodone with sedating H1-blockers can potentiate respiratory depression and/or sedation. In addition, chlorpheniramine and diphenhydramine inhibit CYP2D6, an enzyme responsible for the metabolism of hydrocodone.[4718] Close monitoring for side effects in patients receiving hydrocodone-containing products and chlorpheniramine or diphenhydramine is recommended.

Concomitant use of acetaminophen; hydrocodone with other CNS depressants can potentiate the CNS effects (e.g., sedation) or respiratory depression effects of both agents. CNS depressants include amoxapine, anxiolytics, sedatives, and hypnotics, clozapine, dronabinol, THC, droperidol, entacapone, general anesthetics, sedating H1-blockers, maprotiline, mirtazapine, molindone, nefazodone, olanzapine, opiate agonists, phenothiazines, pimozide, pramipexole, pregabalin, quetiapine, risperidone, ropinirole, skeletal muscle relaxants, tolcapone, tramadol and trazodone. If used concomitantly, the dosage of acetaminophen; hydrocodone and/or the other CNS depressant should be reduced.[6501]

Because diphenhydramine can cause pronounced sedation,[6568] an enhanced CNS depressant effect may occur when it is combined with other CNS depressants [6568] including anxiolytics, sedatives, and hypnotics (such as barbiturates and benzodiazepines) [6946] [6948], buprenorphine [5278], butorphanol [5912], carisoprodol, clozapine [4989], dronabinol, THC, droperidol [5468], entacapone [5769], ethanol [6341] [6948], general anesthetics [6892], haloperidol [5036], methocarbamol, mirtazapine [5366], molindone [5553], nalbuphine [6778], nefazodone [5414], olanzapine [5517], opiate agonists, pentazocine [6777], phenothiazines [6946], pimozide [5250], pramipexole [5640], pregabalin [7523], procarbazine [5356], quetiapine [5855], risperidone [5144], ropinirole [8018], tolcapone [5578], tramadol [5043], trazodone [5450], tricyclic antidepressants [6947], or with other sedating H1-blockers [6568].

Acetaminophen; Hydrocodone (Hydrocodone;Acetaminophen) and Eszopiclone (Lunesta™)

Severity: Moderate

Using eszopiclone with ethanol or other CNS depressants may have cumulative effects and can increase the risk for sedation.[7331] Eszopiclone should not be taken with alcohol. A dose reduction may be necessary if eszopiclone is co-administered with other CNS depressants [7331], such as: antiparkinson's drugs (e.g., entacapone [5769], pramipexole, ropinirole, and tolcapone [5578]); chloral hydrate [6948]; cannabinoids (e.g., dronabinol, THC); droperidol [5468]; general anesthetics; opiate agonists; mixed opiate agonists/antagonists (e.g., buprenorphine [5278], butorphanol [5912], nalbuphine [6778], pentazocine [6969]); pregabalin [7523], psychotropic agents; sedating H1-blockers; tramadol [5043]; tricyclic antidepressants; zaleplon [6634]; zolpidem [6473]; and other anxiolytics, sedatives, and hypnotics (including barbiturates and benzodiazepines).

Acetaminophen; Hydrocodone (Hydrocodone;Acetaminophen) and Acetaminophen (found in Tylenol® PM)

Severity: High

Many prescription and non-prescription medicines contain acetaminophen. Avoid concurrent use of products that contain acetaminophen as the maximum daily dose (e.g., 4 g/day for adults) may be exceeded. High dosages of acetaminophen on a chronic basis can cause depletion of glutathione stores, which can lead to a greater production of the hepatotoxic metabolite, NAPQI.[4925] Advise patients to carefully read the ingredients of any other medicines they are taking with acetaminophen; hydrocodone products.[4925]

Eszopiclone (Lunesta™) and Diphenhydramine (found in Tylenol® PM)

Severity: Moderate

Tacrolimus (Protopic®) and Mometasone (Nasonex®)

Severity: High

Patients receiving tacrolimus and systemic corticosteroids concomitantly should be carefully monitored for alterations in tacrolimus whole blood concentrations. Methylprednisolone is an inhibitor of CYP3A4, therefore inhibiting tacrolimus metabolism and leading to increased tacrolimus blood concentrations.[5342] Conversely, in one study the addition of prednisone or prednisolone to tacrolimus-containing medication regimens resulted in decreased tacrolimus blood concentrations; patients required higher doses of tacrolimus to maintain appropriate tacrolimus blood concentrations.[4509]

Tacrolimus (Protopic®) and Rosuvastatin (Crestor®)

Severity: Moderate

The risk of developing myopathy during therapy with HMG-CoA reductase inhibitors may be increased when used with tacrolimus. Systemic cerivastatin exposure increased 35% after 12 weeks of use with tacrolimus as compared with systemic cerivastatin exposure after the first dose.[6182] The mechanism of the interaction is unknown. The pharmacokinetic parameters of tacrolimus were unaltered.

Calcium Salts (found in Therapeutic Multivitamin with Minerals) and Mometasone (Nasonex®)

Severity: Moderate

Calcium absorption is reduced when calcium salts are taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.[8256] [8255]

Ergocalciferol, Vitamin D2 (found in Therapeutic Multivitamin with Minerals) and Atenolol; Chlorthalidone

Severity: High

Concomitant use of thiazide diuretics and ergocalciferol in patients with hypoparathyroidism can result in hypercalcemia,[6916] which is likely due to increased release of calcium from the bone. This condition may be transient or require discontinuation of the vitamin D analog.

Ergocalciferol, Vitamin D2 (found in Therapeutic Multivitamin with Minerals) and Mometasone (Nasonex®)

Severity: Low

Vitamin D plus calcium supplements are generally recommended for the prevention of osteoporosis in patients taking long-term corticosteroids.[6905] A relationship of functional antagonism exists between vitamin D analogs, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption.[6916] [1441] Therapeutic effect of vitamin D analogs should be monitored when used concomitantly with corticosteroids.

Magnesium Salts (found in Therapeutic Multivitamin with Minerals) and Diphenhydramine (found in Tylenol® PM)

Severity: Low

Because of the CNS-depressant effects of magnesium sulfate [7197], additive central-depressant effects can occur following concurrent administration with barbiturates, opiate agonists, sedating H1-blockers, antidepressants, benzodiazepines, general anesthetics, local anesthetics, and phenothiazines.

Magnesium Salts (found in Therapeutic Multivitamin with Minerals) and Acetaminophen; Hydrocodone (Hydrocodone;Acetaminophen)

Severity: Low

Magnesium Salts (found in Therapeutic Multivitamin with Minerals) and Atenolol; Chlorthalidone

Severity: Moderate

Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of loop diuretics or thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.[7114] Conversely, long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency.

Niacin, Niacinamide (found in Therapeutic Multivitamin with Minerals) and Atenolol; Chlorthalidone

Severity: Moderate

Clonidine has been shown to inhibit niacin-induced flushing.[7631] This interaction is harmless unless niacin augments the hypotensive actions of clonidine. Finally, clinicians should keep in mind that cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents,[5932] especially peripheral vasodilators such as epoprostenol, nitrates, calcium-channel blockers, or others, particularly in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.

________________________________________________________________________________

Adverse Reactions

• abdominal pain (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• acneiform rash (Nasonex®)

• acute generalized exanthematous pustulosis (AGEP) (Hydrocodone;Acetaminophen)

• adrenocortical insufficiency (Nasonex®)

• agitation (Protopic®)

• agranulocytosis (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• alopecia (Protopic® | Atenolol; Chlorthalidone | Crestor®)

• amnesia (Protopic®)

• anaphylactic shock (Cyanocobalamin, Vitamin B12 | Aleve® | Hydrocodone;Acetaminophen)

• anemia (Aleve® | Protopic® | Atenolol; Chlorthalidone | Lunesta™)

• angina (Protopic®)

• angioedema (Aleve® | Allegra® | Hydrocodone;Acetaminophen | Nasonex® | Crestor®)

• anorexia (Protopic® | Hydrocodone;Acetaminophen | Crestor®)

• anxiety (Cyanocobalamin, Vitamin B12 | Protopic® | Lunesta™)

• aplastic anemia (Aleve® | Atenolol; Chlorthalidone)

• arthralgia (Nasonex®)

• aseptic meningitis (Aleve®)

• asthenia (Protopic® | Crestor®)

• ataxia (Cyanocobalamin, Vitamin B12)

• AV block (Atenolol; Chlorthalidone)

• azotemia (Protopic® | Atenolol; Chlorthalidone)

• back pain (Protopic® | Crestor®)

• bleeding (Aleve® | Hydrocodone;Acetaminophen)

• blurred vision (Aleve® | Protopic® | Atenolol; Chlorthalidone)

• bronchospasm (Atenolol; Chlorthalidone | Nasonex®)

• bullous rash (Protopic®)

• candidiasis (Nasonex®)

• cardiac arrest (Hydrocodone;Acetaminophen)

• cardiomyopathy (Protopic®)

• cataracts (Nasonex® | Crestor®)

• chest pain (unspecified) (Protopic® | Nasonex® | Lunesta™)

• chills (Protopic®)

• cholestasis (Crestor®)

• coagulopathy (Protopic®)

• coma (Protopic®)

• confusion (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Lunesta™)

• conjunctivitis (Nasonex®)

• constipation (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Crestor®)

• contact dermatitis (Hydrocodone;Acetaminophen | Nasonex® | Garlic)

• cough (Protopic® | Nasonex®)

• Cushing's syndrome (Nasonex®)

• cystitis (Protopic®)

• dehydration (Protopic®)

• delirium (Protopic®)

• depression (Aleve® | Protopic® | Atenolol; Chlorthalidone | Lunesta™)

• diabetes mellitus (Protopic® | Atenolol; Chlorthalidone)

• diaphoresis (Aleve®)

• drowsiness (Aleve® | Allegra® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Lunesta™)

• dysarthria (Protopic®)

• dysgeusia (Nasonex® | Lunesta™)

• dysmenorrhea (Allegra® | Nasonex® | Lunesta™)

• dysphagia (Aleve®)

• dyspnea (Aleve® | Protopic® | Atenolol; Chlorthalidone | Lunesta™)

• dysuria (Protopic®)

• ecchymosis (Protopic®)

• edema (Aleve® | Hydrocodone;Acetaminophen | Crestor®)

• elevated hepatic enzymes (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• emotional lability (Protopic®)

• encephalopathy (Protopic® | Hydrocodone;Acetaminophen)

• eosinophilia (Aleve®)

• epistaxis (Nasonex®)

• eructation (Garlic)

• erythema (Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Nasonex®)

• erythema multiforme (Aleve® | Lunesta™)

• esophageal stricture (Aleve®)

• esophageal ulceration (Aleve®)

• esophagitis (Aleve®)

• exfoliative dermatitis (Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• fatigue (Aleve® | Protopic® | Allegra® | Atenolol; Chlorthalidone)

• fever (Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Lunesta™ | Crestor®)

• flatulence (Garlic | Crestor®)

• flushing (Protopic®)

• folliculitis (Protopic® | Nasonex®)

• furunculosis (Nasonex®)

• gastritis (Aleve®)

• GI bleeding (Aleve® | Protopic®)

• GI perforation (Aleve® | Protopic®)

• glomerulonephritis (Aleve®)

• gout (Atenolol; Chlorthalidone)

• growth inhibition (Nasonex®)

• gynecomastia (Lunesta™)

• halitosis (Garlic)

• hallucinations (Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Lunesta™)

• hearing loss (Aleve®)

• heart failure (Aleve® | Atenolol; Chlorthalidone)

• hematemesis (Aleve®)

• hematoma (Garlic)

• hematuria (Aleve® | Protopic® | Crestor®)

• hemolysis (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• hemolytic anemia (Aleve® | Protopic® | Hydrocodone;Acetaminophen)

• hemolytic-uremic syndrome (Protopic®)

• hepatic failure (Aleve® | Crestor®)

• hepatic necrosis (Hydrocodone;Acetaminophen | Crestor®)

• hepatitis (Aleve® | Protopic® | Lunesta™ | Crestor®)

• hepatomegaly (Lunesta™)

• hirsutism (Protopic®)

• hyperbilirubinemia (Protopic® | Atenolol; Chlorthalidone)

• hypercalcemia (Protopic® | Atenolol; Chlorthalidone)

• hypercholesterolemia (Protopic® | Atenolol; Chlorthalidone)

• hyperesthesia (Protopic® | Nasonex®)

• hyperglycemia (Protopic® | Atenolol; Chlorthalidone)

• hyperkalemia (Aleve® | Protopic®)

• hyperlipidemia (Protopic®)

• hyperphosphatemia (Protopic®)

• hypertension (Aleve® | Protopic® | Lunesta™)

• hypertonia (Protopic®)

• hypertrichosis (Nasonex®)

• hypertriglyceridemia (Atenolol; Chlorthalidone)

• hyperuricemia (Protopic® | Atenolol; Chlorthalidone)

• hypocalcemia (Protopic®)

• hypoglycemia (Protopic® | Atenolol; Chlorthalidone)

• hypokalemia (Cyanocobalamin, Vitamin B12 | Protopic® | Atenolol; Chlorthalidone)

• hypomagnesemia (Protopic® | Atenolol; Chlorthalidone)

• hyponatremia (Protopic®)

• hypophosphatemia (Protopic®)

• hypoprothrombinemia (Hydrocodone;Acetaminophen)

• hypotension (Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• hypothalamic-pituitary-adrenal (HPA) suppression (Nasonex®)

• ileus (Protopic®)

• impaired wound healing (Nasonex®)

• impotence (Atenolol; Chlorthalidone | Crestor®)

• increased intracranial pressure (Nasonex®)

• insomnia (Aleve® | Protopic® | Allegra® | Crestor®)

• interstitial nephritis (Aleve® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• jaundice (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• leukoencephalopathy (Protopic®)

• leukopenia (Aleve® | Atenolol; Chlorthalidone | Crestor®)

• libido decrease (Lunesta™)

• lymphadenopathy (Protopic®)

• maculopapular rash (Hydrocodone;Acetaminophen | Lunesta™)

• malaise (Aleve®)

• melena (Aleve®)

• metabolic acidosis (Protopic®)

• metabolic alkalosis (Protopic®)

• methemoglobinemia (Hydrocodone;Acetaminophen)

• migraine (Lunesta™)

• miliaria (Nasonex®)

• miosis (Hydrocodone;Acetaminophen)

• muscle cramps (Atenolol; Chlorthalidone | Crestor®)

• musculoskeletal pain (Nasonex®)

• myalgia (Nasonex® | Crestor®)

• myasthenia (Aleve® | Crestor®)

• myoclonia (Protopic®)

• myoglobinuria (Crestor®)

• myopathy (Lunesta™)

• nasal irritation (Nasonex®)

• nasal septum perforation (Nasonex®)

• neonatal abstinence syndrome (Hydrocodone;Acetaminophen)

• nephrolithiasis (Atenolol; Chlorthalidone)

• nephrotic syndrome (Aleve®)

• neutropenia (Aleve® | Hydrocodone;Acetaminophen)

• nightmares (Atenolol; Chlorthalidone)

• nocturia (Protopic®)

• ocular hypertension (Nasonex®)

• odynophagia (Aleve®)

• oliguria (Protopic®)

• orthostatic hypotension (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• otalgia (Nasonex®)

• palpitations (Hydrocodone;Acetaminophen)

• pancreatitis (Aleve® | Atenolol; Chlorthalidone | Crestor®)

• pancytopenia (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• papilledema (Nasonex®)

• paresthesias (Cyanocobalamin, Vitamin B12 | Protopic® | Nasonex®)

• peptic ulcer (Aleve®)

• periarteritis (Atenolol; Chlorthalidone)

• peripheral edema (Aleve® | Protopic® | Lunesta™)

• pharyngitis (Nasonex® | Crestor®)

• phlebitis (Protopic®)

• photophobia (Aleve® | Protopic®)

• photosensitivity (Aleve® | Protopic® | Atenolol; Chlorthalidone)

• physiological dependence (Hydrocodone;Acetaminophen)

• platelet dysfunction (Aleve®)

• pneumonitis (Aleve®)

• polycythemia (Protopic®)

• proteinuria (Crestor®)

• pseudoporphyria (Aleve®)

• psoriaform rash (Atenolol; Chlorthalidone)

• psoriasis (Atenolol; Chlorthalidone)

• psychosis (Protopic® | Atenolol; Chlorthalidone)

• pulmonary edema (Cyanocobalamin, Vitamin B12)

• purpura (Aleve® | Hydrocodone;Acetaminophen | Nasonex® | Crestor®)

• pyrosis (heartburn) (Aleve® | Garlic)

• pyuria (Protopic®)

• QT prolongation (Protopic® | Allegra®)

• renal failure (unspecified) (Aleve® | Protopic® | Hydrocodone;Acetaminophen | Crestor®)

• renal papillary necrosis (Aleve® | Hydrocodone;Acetaminophen)

• renal tubular necrosis (Protopic® | Hydrocodone;Acetaminophen)

• renal tubular obstruction (Crestor®)

• respiratory depression (Hydrocodone;Acetaminophen)

• restlessness (Allegra® | Hydrocodone;Acetaminophen | Lunesta™)

• rhabdomyolysis (Crestor®)

• rhinitis (Cyanocobalamin, Vitamin B12 | Nasonex® | Crestor®)

• secondary malignancy (Protopic®)

• seizures (Protopic®)

• sialadenitis (Atenolol; Chlorthalidone)

• sinus bradycardia (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• sinusitis (Protopic® | Nasonex® | Crestor®)

• skin atrophy (Nasonex®)

• skin discoloration (Protopic®)

• skin irritation (Protopic® | Nasonex®)

• skin ulcer (Protopic® | Nasonex®)

• Stevens-Johnson syndrome (Aleve® | Atenolol; Chlorthalidone | Crestor®)

• stomatitis (Aleve® | Protopic®)

• syncope (Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone)

• telangiectasia (Nasonex®)

• teratogenesis (Atenolol; Chlorthalidone)

• thrombocytopenia (Aleve® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• thrombocytosis (Cyanocobalamin, Vitamin B12 | Hydrocodone;Acetaminophen)

• thrombosis (Protopic®)

• tinnitus (Aleve® | Protopic®)

• tolerance (Hydrocodone;Acetaminophen | Nasonex®)

• torsade de pointes (Protopic®)

• toxic epidermal necrolysis (Aleve® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• tremor (Protopic®)

• urinary incontinence (Protopic®)

• urticaria (Aleve® | Allegra® | Hydrocodone;Acetaminophen | Atenolol; Chlorthalidone | Crestor®)

• vasculitis (Aleve®)

• vertigo (Aleve® | Atenolol; Chlorthalidone)

• visual impairment (Aleve® | Atenolol; Chlorthalidone)

• weight gain (Protopic®)

• wheezing (Atenolol; Chlorthalidone)

• withdrawal (Hydrocodone;Acetaminophen | Nasonex®)

• xanthopsia (Atenolol; Chlorthalidone)

• xerophthalmia (Atenolol; Chlorthalidone)

• xerosis (Nasonex®)

• xerostomia (Atenolol; Chlorthalidone | Lunesta™)

________________________________________________________________________________

Precautions

Precaution: Aleve® in hypertension

Due to the role of prostaglandins in renal function and hemodynamics, patients with renal disease or at risk for renal disease should be closely observed during therapy with naproxen due to an increased risk for reduced renal blood flow or volume. Naproxen and its metabolites are renally excreted. Accumulation of parent drug and metabolites can occur in patients with renal disease, renal impairment or renal failure, increasing the risk of potential toxicity. Dosage adjustment may be necessary (see Dosage, renal impairment). Conditions such as congestive heart failure, edema, or hypertension can be exacerbated by the fluid retention cause by suboptimal renal perfusion. Naproxen should be used cautiously in patients with any of these conditions or other diseases that predispose to fluid retention. Meta-analysis have demonstrated that the effect of NSAIDs on blood pressure is the greatest in hypertensive individuals receiving antihypertensive medication. In addition, normotensive patients receiving antihypertensive therapy had higher increases in blood pressure than subjects with uncontrolled hypertension or normotensive subjects receiving no hypertensive therapy.[4087] Patients with renal impairment, renal failure, hepatic disease, diabetes mellitus, systemic lupus erythematosus (SLE), or congestive heart failure, rheumatoid arthritis, edema, extracellular volume depletion (i.e., hypovolemia or dehydration), sepsis; those taking diuretics or nephrotoxic drugs; and the elderly are at the highest risk for complications related to suboptimal renal perfusion. Also, the elderly have an increased free plasma fraction of naproxen relative to younger adult patients, which may be associated with a greater risk of adverse effects at a given dosage (see Pharmacokinetics).

Precaution: Aleve® in renal impairment

Precaution: Allegra® in renal impairment

Fexofenadine should be used cautiously in patients with renal impairment associated with renal disease or renal failure. Peak plasma concentrations were 87% and 111% greater in patients with mild (CrCl 41-80 ml/min) to severe (CrCl 11-40 ml/min) renal impairment, respectively. Mean elimination half-lives were 59% and 72% longer, respectively, than in normal volunteers. Peak plasma concentrations in dialysis patients (CrCl <= 10 ml/min) were 82% greater and half-life was 31% longer than in normal volunteers. Patients with mild to severe renal impairment should be given half the initial dose due to reduced clearance of fexofenadine.

Precaution: Atenolol; Chlorthalidone in hypercholesterolemia

Thiazide diuretics and beta-blockers may worsen hypertriglyceridemia and hypercholesterolemia. The clinical implications of these effects, relative to the cardiovascular benefits of therapy, are not known. Serum cholesterol and triglyceride concentrations should be monitored periodically in hypertensive patients receiving atenolol; chlorthalidone.

Precaution: Atenolol; Chlorthalidone in renal impairment

Atenolol; chlorthalidone is contraindicated in patients with anuria since thiazide-like diuretics are considered ineffective when the creatinine clearance is less than 30 ml/minute. Chlorthalidone should be used cautiously in patients with renal disease that produces renal failure or severe renal impairment because the drug decreases the glomerular filtration rate and may precipitate azotemia in these patients. Reduced doses of atenolol should be used in patients with renal impairment because of reduced excretion of the drug.

Precaution: Crestor® in renal impairment

Rosuvastatin has been approved by the FDA for the dosage range of 5-40 mg PO once daily. The manufacturer originally intended to seek approval for an 80 mg dose; however, two patients developed renal toxicity (e.g., rhabdomyolysis, renal dysfunction) while receiving this dose. On July 9th 2003, an FDA advisory committee recommended monitoring renal function in patients receiving the highest rosuvastatin dosage of 40 mg/day based on findings of increased frequency of hematuria and proteinuria (1.3%). Despite the Advisory Committee recommendation, the final labeling only provides a precaution to reduce rosuvastatin dosage in patients receiving the 40 mg/day dosage who have unexplained persistent proteinuria during routine urinalysis testing. Relative to other statins, a significant percentage (28%) of rosuvastatin is excreted renally. Rosuvastatin serum concentrations are increased approximately 3-fold in patients with severe renal impairment (CrCl < 30 ml/min) vs. patients with normal renal function. Lower rosuvastatin dosage is recommended for patients with CrCl < 30 ml/min (see Dosage). According to the manufacturer, hemodialysis does not significantly enhance the clearance of rosuvastatin. Rosuvastatin serum concentrations are increased approximately 50% in hemodialysis vs. patients with normal renal function. Rosuvastatin should be used with caution in patients with pre-existing significant renal impairment who are generally at a higher risk of developing rhabdomyolysis during therapy with HMG-CoA reductase inhibitors. Several drugs are known to increase the risk of myopathy and rhabdomyolysis associated with HMG-CoA reductase inhibitors (see Drug Interactions). Since rosuvastatin undergoes minimal hepatic metabolism, the potential for drug interactions is expected to be less than with 'statins' metabolized by CYP3A4 isoenzymes such as atorvastatin, cerivastatin, lovastatin, and simvastatin.[3797] [3798] Rhabdomyolysis has been associated with HMG-CoA reductase therapy alone, when combined with immunosuppressive therapy including cyclosporine in transplant patients, and when combined in non-transplant patients with either gemfibrozil, lipid-lowering doses of nicotinic acid, or with the antifungal agent itraconazole. Because renal failure is possible if rhabdomyolysis occurs, HMG-CoA reductase inhibitors should be used with caution in patients with conditions that can cause decreased renal perfusion. Predisposing conditions for decreased renal perfusion include renal disease or renal insufficiency, diabetes mellitus, hypotension, acute infection, endocrine disease, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Rosuvastatin should be discontinued immediately in any patient who develops myopathy, elevations in creatine kinase (CK), or evidence of a drug-induced decrease in renal function. On March 2, 2005, the FDA issued a public health advisory warning that rhabdomyolysis has been reported in patients taking rosuvastatin as well as other HMG-CoA reductase inhibitors. The risk for myopathy/rhabdomyolysis, is increased at higher doses (e.g., 40 mg/day). The current labeling recommends that the 40 mg dose of rosuvastatin be reserved only for those patients who have not achieved their LDL-C goal utilizing the 20 mg dose once daily. Rosuvastatin should be discontinued immediately in any patient who develops myopathy or evidence of rhabdomyolysis.

Precaution: Hydrocodone;Acetaminophen in renal impairment

Acetaminophen-hydrocodone should be used cautiously in patients with renal impairment or renal failure; dosage adjustments may be required. Hydrocodone can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction or pelvic tumors. In addition, hydrocodone may accumulate in these patients leading to a prolonged duration of action and potential increase in side effects. Chronic acetaminophen administration should be avoided in patients with underlying renal disease; however it may be used for episodic pain.

Precaution: Protopic® in hypertension

Systemic tacrolimus should be used cautiously in patients with pre-existing hypertension. Tacrolimus therapy is associated with mild or moderate hypertension, but can also cause severe hypertension. Antihypertensive therapy may be required. Potassium-sparing diuretics should be avoided since tacrolimus can cause hyperkalemia. Additionally, use calcium-channel blockers cautiously because some may interfere with tacrolimus metabolism (see Drug Interactions). To prevent electrolyte imbalance, serum potassium as well as other serum electrolytes should be monitored during tacrolimus therapy.

Precaution: Protopic® in renal impairment

Systemic tacrolimus therapy is associated with significant nephrotoxicity. Patients with preexisting renal disease or renal impairment should be carefully monitored for further deterioration in renal function while receiving tacrolimus. In renal transplant patients, tacrolimus therapy should be delayed up to 48 hours or longer in patients with post-operative oliguria or renal failure (i.e., serum creatinine >= 4 mg/dl). Monitor these patients carefully; lower tacrolimus doses may be warranted. In patients who develop renal failure while receiving tacrolimus, echocardiographic evaluation should be considered. Avoid concurrent use of nephrotoxic drugs, especially cyclosporine (see Drug Interactions). Whole blood levels of tacrolimus should be monitored frequently in these patients.