NEW! Sample Consult No.3

Patient Profile for Browning, Dennis R.

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General Information

ID: drb05232005

Prescriber: LaMont, Harold, M.D.

Name: Browning, Dennis R.

Address: 107 Bass Street.

City: Panacea

State: FL

Zip: 34339

Country: USA

Phone: 850.348.3829

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Current Conditions

• allergic rhinitis

• benign prostatic hyperplasia (BPH)

• bipolar disorder

• bone pain

• constipation

• depression

• diarrhea

• headache

• hypercholesterolemia

• hypogonadism

• local anesthesia

• muscle spasm

• neuropathic pain

• nutritional supplementation

• osteoarthritis

• Parkinson's disease

• renal impairment

• severe pain

• vertebral disc herniation

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Current Allergies

No allergies noted

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Current Medications

• Medication

• Amidrine® Sig: tab 1 every four hours as needed for headache

• Androderm® Dosage: 5mg Sig: patch 1 daily

• Benadryl® Dosage: 25mg Sig: two as needed for runny nose

• Celexa® Dosage: 40mg Sig: two in AM

• Chondroitin; Glucosamine Dosage: 500mg/400mg Sig: 1 three times a day

• Colace® Dosage: 100mg Sig: three after dinner

• Depakote® Dosage: 500mg Sig: three times a day

• Effexor® XR Dosage: 150mg Sig: two AM and 1 PM

• Fish Oil, Omega-3 Fatty Acids Dosage: 1000mg Sig: 1 three times a day

• Flexeril® Dosage: 10mg Sig: 1 every 8 hours as needed for muscle spasms

• GlycoLax™ Dosage: 17mg Sig: 17mg daily

• Imodium® Dosage: 2mg Sig: 2 as needed for diarrhea

• Lamictal® Dosage: 100mg Sig: 1 in AM

• Lidoderm® Dosage: 5mg patch Sig: apply for 12 hours.. remove for 12 hours and repeat

• Lipitor® Dosage: 40mg Sig: 1 at bedtime

• Mirapex® Dosage: 1mg Sig: 1 at bedtime

• Morphine Dosage: 30mg Immediate Release Sig: 1 four times a day

• Morphine Dosage: 30mg Extended Release Sig: 1 twice a day

• Psyllium Dosage: 500mg Sig: 3 two times a day

• Saw Palmetto Dosage: 900mg Sig: tab 2 twice a day

• Skelaxin® Dosage: 800mg Sig: tab 1 three times a day... (omit Flexeril)

• Vitamin C Dosage: 500mg Sig: 1 daily

• Vitamin E Dosage: 400 Units Sig: 1 daily

• Zetia® Dosage: 10mg Sig: 1 in AM

• Zyprexa® Dosage: 10mg Sig: tab 1 at bedtime

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Dosing Parameters

Gender: Male

Birthdate: 1/2/1938

Weight: 75.91 kgs

Height: 172.72 cm

Ideal Body Weight: 68.61 kgs

Body Surface Area: 1.91 m²

Serum Creatinine: 1.1 mg/dL

Creatinine Clearance: 63.24 mL/min

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Notes

Title: Initial Interview & Assessment

Date: 08/03/2005

This 67 year old white male presents with a long list of complaints and is currently on 24 different medications daily. He is in pain and frustrated with his current physical condition. He has suffered from severe back injuries and pain for several years. Efforts to try to control the pain have not been too successful. The inclusion of osteoarthritis of course adds to the problems with pain and mobility. He has had over the years multiple surgeries on his back and spine. An assessment using the Geriatric Depression Scale shows a score of 5 which places the patient in depression and anxiety. He currently is on several SSRI s, muscle relaxants, and antipsychotic drugs concomitantly. Use of Dopamine agonists, Mirapex, is not consistent with concomitant use of dopamine antagonists. Discussions with his wife during the interview revealed that the patient is in constant movement throughout the night. I am not surprised, with several SSRI drugs currently being used, and the antipsychotic drug all concomitantly place the patient at very high risk for tardive dyskinesia and other movement disorder problems such as serotonin syndrome. Concomitant use of testosterone patch and Saw Palmetto contradicts each other and places potential for therapeutic benefits from either at a low level. Concomitant use of two muscle relaxants, Flexeril and Skelaxin, both anticholinergic type drugs, are not recommended with other drugs currently being used. The use of these muscle relaxants combined with anticholinergic Benadryl surely does increase problems with constipation for which several medications are used. This constipation problem is also exacerbated by the use of the opiates currently used to control pain. Another problem with the muscle and joint pain may be due to the multiple use of statin Lipitor and Zetia. Just by nature of age sarcopenia is always present in the geriatric patient and becomes more dominant as we age. When drugs such as statin drugs are used, especially on a patient with numerous physical problems, rhabdomyolysis can exacerbate the muscle deterioration and lead to serious problems including liver and renal failure. The concomitant use of Lamictal and Depakote are contraindicated and the depakote will more than double the elimination half life of the Lamictal which makes many of the complaints subject to adverse events consistent with the Lamictal. A consolidation of many of these drugs is necessary for numerous health reasons and quality of life issues. I will discuss the various nutraceuticals in the recommendations section.

Title: Drug Therapy Evaluation & Recommendations

Date: 08/03/2005

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

Amidrine - an old combination of drugs used to treat migraine headaches but portions of the drug conflict with other drugs currently being consumed. I do not find any value from continued use of this drug. This drug should be discontinued.

Androderm - use of testosterone patch comes with a long list of adverse events. The list varies from insomnia, headache, hepatic problems, BPH and myopathy. I believe until we have the overall drug therapy management under some kind of control this drug should be tapered off over the next month and wait and see if it is needed in 60 to 90 days.

Benadryl - use of anticholinergic antihistamine drugs are contraindicated in the geriatric patient and with all the other anticholinergic drugs currently consumed it should be discontinued at once. Use of non-anticholinergic Claritin or Zyrtec daily could be an alternative treatment for allergy symptoms.

Celexa - 80mg daily of this SSRI is an excessive dose. Used along with 450mg of Effexor XR another SSRI makes the current dose extremely excessive and will lead to involuntary movement disorders and many serious side effects. It is apparent that the antiepileptic drugs currently used to help control mood are not effective and many changes should be made in this therapy which I will discuss. A tapering starting with the Celexa is needed until it is discontinued, then a continuation of tapering of Effexor XR along with changes in the antiepileptic medications are going to be necessary to reach our mutual goal. This tapering process may not be pleasant since be body is acclimated to all this additional chemistry.

Chondroitin/Glucosamine - many studies show a high degree of benefits from the use of this drug in joint and muscle pain. A total of 1200mg Chondroitin and 1500mg of Glucosamine are required daily for therapeutic benefits. Some places have a “triple strength” size dose that will allow for two tablets to be taken each morning and the therapeutic parameters are met.

Colace - use of this stool softener I am sure is necessary due to the enormous amounts of anticholinergic drugs and opiates consumed each day. After we have tapered you off many of these unnecessary drugs, there should be a reduction in the amounts of stool softeners.

Depakote - Although 1500mg daily should benefit you, I question whether it really does, or are the effects simply subdued due to all the other contradicting medications you are currently taking.

Effexor XR - an excellent antidepressant-anxiolytic drug SSRI-SNRI action is probably needed but dose is excessive and contraindicated in view of others being used and numerous other medications that effect motor function. The use of this drug will probably be needed but in much smaller dosing.

Fish Oil - I am a firm believer in the use of antioxidants and this is an extra good choice. Continuation of this is encouraged.

Flexeril - Use of anticholinergic drugs in the geriatric patient is contraindicated due to other serious adverse events. This is also a contributing factor in your constipation problem. This drug needs to be tapered and discontinued eventually. If not taking routinely then it should not be taken any more.

Glycolax - another laxative that may be reduced or stopped once we reduce the overall drug therapy on the patient.

Lamictal - 100mg daily dose due to chemical changes in bioavailability by concomitant use of the Depakote will double the activity of the drug. Because of this all the complaints listed in this patient are potential adverse events associated with this drug incompatibility. This drug needs to be stopped and alternative methods to treat bipolar problems pursued. I will discuss this in my recommendations in detail.

Lidoderm - use of this drug is for off label reasons and places a seriously high risk of cardiac problems, cardiovascular collapse and probably cardiac arrest. The depth of the pain areas in your back exceed the distance that this peripheral nerve block drug will work.

Lipitor - with review of your lipid profile and the degree of pain you current endure I believe that a trial of assuming elevated homocystine and methylmelanonic acid levels and treating as such and reevaluate lipid profile in 4 months. The use of Vitamin B12 injection, B6 and Folic acid normally reduces cholesterol and LDL in most patients without the need for statin therapy. This greatly reduces the risk of rhabdomyolysis and liver and kidney failure.

Mirapex - use of this dopamine agonist is unnecessary in this patient. It is being used to treat side effects associated with the anticholinergic, antipsychotic and other psychoactive drugs. Making drastic modifications in these therapies will reduce these side effects. Actual benefit from continued use of this drug is none.

Morphine - use of this most potent opiate agonist may be necessary but I have great concerns that continued use at these dose levels will only lead to higher and higher dosing and serious adverse events and addiction. Also, the use of this drug in the amounts prescribed exacerbates more constipation problems. If at all possible some other means should be explored. I am well aware of the discomfort in making changes in this drug to some other pain control but attempts should be made. Use of Fentanyl patches may be an alternative and should be given a fair chance to see if success can be derived. Use of these patches give 24hour pain relief without the peaks and troughs now experienced with the morphine oral dosing. This may be a good alternative.

Psyllium - another laxative which may be stopped after adjustment of drug therapy. I am sure it is necessary at the present just from review of current drug regimen.

Saw Palmetto - use of this drug with testosterone patch is contraindicated and each negate any therapeutic benefits for each. Both the testosterone patch and Saw Palmetto should be discontinued. Use of Proscar has fewer side effects and will control problems from BPH,. although you may not have BPH after a few months off the testosterone patch.

Skelaxin - a very heavy anticholinergic drug that only exacerbate numerous problems listed with this patient. This drug should be stopped.

Vitamin C - use of antioxidants is necessary for the geriatric but at this dose little benefit can be received. The patient should continue Vitamin C but at 2GM dosing daily

Vitamin E - although some studies show no benefit from use of vitamin E they were done on mega dosing. The use of 400U daily works as an antioxidant and should be continued.

Zetia - Use of cholesterol lowering drugs may not be necessary and a rest period is needed to determine how much contribution they have with the current adverse events currently being experienced.

Zyprexa - after discussion with the patient’s wife it is apparent that this highly anticholinergic antipsychotic drug is becoming a problem. Unintended movements are the first signs of the beginning of irreversible tardive dyskinesia. There is no diagnosis or condition that requires the need for antipsychotic drug therapy. This drug needs to be tapered and discontinued.

Drug Therapy Management

Stop Amidrine

Stop Androderm patch (taper 5mg every other day for 30 days and discontinue)

Stop Benadryl

Stop Celexa (taper 40mg in AM for 14 days, then every other day for 14 days and stop)

Stop Flexaril

Stop Skelaxin (taper twice a day for 7 days, once a day for 7 days, every other day for 7 days and discontinue

Stop Lamictal ( taper 50mg every day for 7 days then 50mg every other day for 7 days then discontinue)

Stop Lidoderm patch (taper apply every other day for 10 days and discontinue)

Stop Lipitor

Stop Mirapex (taper 1mg every other bedtime for 7 days and discontinue)

Stop Morphine (see dosing schedule listed below)

Stop Saw Palmetto

Stop Zetia

Stop Zyprexa ( taper 5mg at bedtime for 30 days, then 2.5mg at bedtime for 30 days, then 2.5mg every other bedtime for 30 days and discontinue

New Drug Therapy

Start:

Vitamin B12 1000mcg IM weekly for 4 weeks then monthly

Vitamin B6 200mg tablet daily

Folic Acid 1mg tablet daily

Zyrtec 10mg tablet daily as needed for allergies

Proscar 5mg tablet daily

Vitamin C 1000mg tab 2 each morning

Fish Oil 1000mg each morning

Vitamin E 400U each morning

Chondroitin/Glucosamine Triple Strength tab 2 each AM

Centrum Silver (or store like brand) tab 1 daily

Fentanyl Patch 25mcg apply every 3 days.. then taper Morphine Immediate Release to

30mg twice a day for 6 days then 30mg each morning for 6 days then 30mg every

other day for 6 days and stop) If breakthroughs are observed increase Fentanyl

patch to 50mcg every 3 days.

After 21 days start taper of Morphine 30mg extended release daily for 6 days, then

every other day for 6 days and discontinue. If breakthrough pain is observed

increase Fentanyl patch to 100mcg every 3 days.

Topamax 25mg daily and taper Depakote to 500mg twice a day for 7 days, then

Increase Topamax to 50mg daily and taper Depakote to 500mg daily for 7 days

then increase Topamax to 100mg daily and discontinue Depakote. If symptoms

continue increase Topamax in 25mg increments to a maxium of 200mg daily.

Effexor XR 150mg twice a day for 30 days, then Effexor XR 150mg at bedtime only

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. I can assure you that coming off some of these drugs is not going to be fun. It is going to take a lot of self restraint on your part to make it happen. I can only design you a pathway to follow. I do know that continued use of the current drug therapy is going to lead to serious and life threatening results. I have seen some excellent outcomes for the combination of Topamax and Effexor XR and side effects are low. I am sure you are in a serotonin syndrome just based on the amount of antidepressants you are taking. I also am sure you need some help from this class of drug, just more realistic dosing. As we move away from all these drugs I am sure other problems may occur and when they do call me and we can make alterations and changes until we get your right dose. It is essential for you to follow the schedule .

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 and reevaluation around the end of September or the first of October but would like a progress report weekly by phone.

Title: Additional Information and Recommendations:

Date: 08/31/2005

A discussion with Mrs. Browning today over e-mail presented with the following questions and problems:

Use of Fentanyl patch has been approved by the Pain Specialist. The drug is on order and tapering of the Morphine dosing will begin as soon as the drug is delivered.

There are concerns over cooperation with the Psychiatrist who Mr. Browning will visit on September 6, 2005. It is necessary that the suggested changes occur as outlined in the report for a successful outcome. I indicated to Mrs. Browning my willingness to talk to the doctor if he would like further explanations.

There are concerns over the use of Vitamin E as it relates to recent studies showing possible harm from its use. These studies were done on mega doses of vitamin E and do not pertain to doses in the 400 to 800 units a day range. Vitamin E is an excellent antioxidant and used in appropriate dosing can provide excellent benefits in fighting cardiovascular disease and high lipids. The dose recommended is well within those parameters considering some you will find in other nutritional supplements recommended.

The correct Vitamin C product to use was also discussed. Although Rose Hips is a natural Vitamin C found in wild roses most commercial products that contain Rose Hips actually only contain minimal amounts. Although is sounds good to advertise Rose Hips in the product the amount normally contained in them provides no extra benefit. Just a regular CVS store brand Vitamin C, time release or not, consuming 2000mg each morning will meet the patient’s needs.

Concerns over the microgram and milligram in understanding dosing of some products that contain folic acid was discussed. I explained that it takes 1000 micrograms to make 1 milligram or that a microgram is one-thousandth of a milligram. Use of the 1mg Folic Acid recommended had taken into consideration other sources of Folic Acid. All the recent studies of the importance of Folic Acid in cognition, anemia and motor function in the geriatric patient makes a compelling case for maintaining high serum folate levels. High folate levels in the geriatric patient is a value that I believe is essential.

Concerns over stopping the Amidrine used for headaches and what to use in its place are an issue. I want to reiterate my recommendation. Side effects are high with the use of Amidrine in the geriatric patient. Some of these adverse events are currently being experienced by the patient, and that further supports discontinuing this therapy. The use of Tramadol plus acetaminophen should support his headache pain management with no problems. I advise the use of Tramadol 50mg plus acetaminophen 500mg every 4 to 6 hours as needed for mild to severe headaches.

I would like a follow-up call after your doctor visit on September 6, 2005.

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Drug Interactions

Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®) and Diphenhydramine (Benadryl®)

Severity: Moderate

Acetaminophen; dichloralphenazone; isometheptene contains the central nervous system depressant dichloralphenazone. The CNS depressant effects can be potentiated by ethanol or other CNS depressants including anxiolytics, sedatives, and hypnotics (including barbiturates and benzodiazepines), antipsychotics, buprenorphine, butorphanol, dronabinol, THC, entacapone, nalbuphine, opiate agonists, pentazocine, phenothiazines, pregabalin [7523], tolcapone, tramadol, tricyclic antidepressants, and sedating H1-blockers. In addition, dichloralphenazone is metabolized to chloral hydrate. A mutual inhibition of metabolism exists between ethanol and chloral hydrate. In rare instances, a disulfiram-like effect, characterized by tachycardia, palpitations, facial flushing, and dysphoria, has occurred with concomitant use of ethanol and chloral hydrate. Further, chronic ethanol use increases acetaminophen-induced hepatotoxicity by inducing cytochrome P450 (CYP) 2E1 leading to increased formation of the hepatotoxic metabolite and by depleting liver glutathione stores. Administration of acetaminophen should be limited or avoided altogether in alcoholics or patients who consume ethanol regularly. However, acute ethanol ingestion may reduce acetaminophen-induced hepatotoxicity by substrate competition for CYP2E1.

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 [5681], tolcapone [5578], tramadol [5043], trazodone [5450], tricyclic antidepressants [6947], or with other sedating H1-blockers [6568].

Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®) and Morphine

Severity: Moderate

Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness. Severe hypotension may occur if morphine is administered to a patient taking a CNS depressant that inhibits blood pressure maintenance such as phenothiazines or general anesthetics. Examples of other CNS depressants include amoxapine; anxiolytics, sedatives, and hypnotics [5897]; clozapine; dronabinol, THC; droperidol [5897]; entacapone; ethanol [5897]; sedating H1-blockers; haloperidol; maprotiline; mirtazapine; molindone; nefazodone; olanzapine; other opiate agonists; pimozide; pramipexole; quetiapine; risperidone; ropinirole; skeletal muscle relaxants [5897]; tolcapone; tricyclic antidepressants; and trazodone. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended.[7186] The impact of additive CNS depression may be dramatic if morphine is used concurrently with chlorpromazine or methocarbamol, as both chlorpromazine or methocarbamol are alkalizing agents. In general, effects of morphine may be potentiated by alkalizing drugs and antagonized by acidifying drugs.[7187]

Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®) and Olanzapine (Zyprexa®)

Severity: Moderate

Other drugs that can cause CNS depression, if used concomitantly with olanzapine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.[5517] Besides ethanol, clinicians should use other anxiolytics, sedatives, and hypnotics (including barbiturates) [5517], buprenorphine [5517], butorphanol [5517], dronabinol, THC [5517], nalbuphine [5517], opiate agonists [5517], pentazocine [5517], tramadol [5043], and trazodone [5517] cautiously with olanzapine.

Testosterone (Androderm®) and Saw Palmetto, Serenoa repens (Saw Palmetto)

Severity: High

Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects.[1797] [6195] The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.

Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto may inhibit 5 alpha-reductase to prevent the conversion of testosterone to dihydrotestosterone.[1797] [6222] This action is similar to the action of 5-alpha reductase inhibitors (i.e., dutasteride, finasteride). Co-use of these agents is likely to be common by patients, but the effects of co-use are not known. In theory, the effects could be additive, but it is not known if the added effects would be beneficial or harmful. Clinicians should be alert for any unusual effects if patients ingest saw palmetto supplements while taking 5-alpha reductase inhibitors.

Diphenhydramine (Benadryl®) and Morphine

Severity: Moderate

Diphenhydramine (Benadryl®) and Cyclobenzaprine (Flexeril®)

Severity: Moderate

The anticholinergic effects of diphenhydramine may be significant and may be enhanced when combined with antimuscarinics [6338]. Other commonly used drugs with moderate to significant anticholinergic effects include amantadine, amoxapine, clozapine, cyclobenzaprine, disopyramide, maprotiline, olanzapine, orphenadrine, most phenothiazines, and most tricyclic antidepressants. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. With many of the listed agents, additive drowsiness may also occur when combined with sedating antihistamines.

Cyclobenzaprine may cause additive CNS depression,[5155] if used concomitantly with other CNS depressants. such as anxiolytics, sedatives, and hypnotics, benzodiazepines, barbiturates, opiate agonists, buprenorphine, butorphanol, nalbuphine, pentazocine, tricyclic antidepressants, phenothiazines, dronabinol, THC, ethanol [6341], or H1-blockers. The phytomedicinal herbs valerian, Valeriana officinalis or kava kava, Piper methysticum may also interact in this fashion. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.

Cyclobenzaprine is structurally very similar to tricyclic antidepressants such as amitriptyline.[5155] Concurrent use should be avoided when possible due to the potential for adverse effects resulting from similar pharmacology.[5155] Like amitriptyline, cyclobenzaprine possesses antimuscarinic properties. If used with other drugs with antimuscarinic properties, anticholinergic side effects can be additive. Examples of drugs that should be used cautiously with cyclobenzaprine for this reason include: amoxapine [5288]; atropine, dicyclomine and other antimuscarinics [6338]; bupropion [4781]; clozapine [4989]; most tricyclic antidepressants; maprotiline [5491]; most antipsychotic phenothiazines; and sedating H1-blockers. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.

Diphenhydramine (Benadryl®) and Olanzapine (Zyprexa®)

Severity: Moderate

Olanzapine exhibits anticholinergic effects that may be clinically significant.[5517] Clinicians should keep this in mind when using antimuscarinics [6338] and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include amantadine [4771], amoxapine [5288], cyclobenzaprine [5155], disopyramide [4954], maprotiline [5491], sedating H1-blockers [3324], orphenadrine [5982], and most tricyclic antidepressants [5294]. Olanzapine may also cause additive sedation [5517] with many of these drugs.

Diphenhydramine (Benadryl®) and Pramipexole (Mirapex®)

Severity: Moderate

The use of ethanol, other parkinson's medications (e.g., entacapone or tolcapone), opiate agonists, buprenorphine, butorphanol, dronabinol, THC, nalbuphine, pentazocine, or anxiolytics, sedatives, and hypnotics in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.[7757]

Citalopram (Celexa®) and Morphine

Severity: Moderate

Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists [4718] (i.e., methadone, morphine, and oxycodone). In addition, impairment of CYP2D6 metabolism by citalopram may reduce the conversion of the opiates codeine and hydrocodone to their active forms, thus reducing analgesic efficacy. Citalopram should also be used cautiously in conjunction with meperidine, as meperidine blocks the neuronal reuptake of serotonin. A 42 year-old man became agitated, restless, diaphoretic, tachycardiac, and hypertensive immediately after receipt of meperidine [4492] 50 mg intravenously. Two weeks before the incident, the patient had stopped a regimen of the SSRI, fluoxetine. Serotonin syndrome was suspected, as fluoxetine and norfluoxetine have long half-lives, and previous meperidine receipt during a time when the patient had not been taking fluoxetine was uneventful.[4492]

Citalopram (Celexa®) and Venlafaxine (Effexor® XR)

Severity: Very High. This drug combination should be avoided.

Citalopram selectively inhibits the reuptake of serotonin, resulting in elevated levels of serotonin in the CNS.[4996] Because of the potential severity of the serotonin syndrome, caution should be observed when administering citalopram with other drugs that have CNS serotonergic properties.[4996] Examples of these drugs include: buspirone [5231] [6261]; cocaine [6160]; lithium [4996]; nefazodone [5414]; trazodone [5450] [5320]; other selective serotonin reuptake inhibitors (SSRIs) [5332] (duplication of therapy); venlafaxine [5002]; tryptophan, 5-HT [5738] [5918]; and St. John's wort, Hypericum perforatum [4935]. The manufacturer reports no pharmacokinetic interaction between lithium and citalopram. However, patients receiving citalopram together with any of these serotonergic agents should be monitored closely for excessive adverse effects.

There may be a potential for rare drug interactions between metoclopramide and selective serotonin reuptake inhibitors (SSRIs) and selected other drugs that inhibit serotonin reuptake (i.e., venlafaxine).[5353] [5371] [5372] The few published case reports of possible interactions have resulted in either 'serotonin-syndrome' type events and/or movement disorders (e.g., dystonia). The mechanism of the interactions is elusive but is thought to be a pharmacodynamic interaction; the interactions do not appear common. In most of the cases reported, a singular drug effect was not ruled out; however, the time course of the events are enough to raise suspicion that a drug interaction might be possible. Patients receiving metoclopramide concomitantly with an SSRI or venlafaxine should report any unusual movements or other unusual side effects to their health care professionals promptly.

Valproic Acid, Divalproex Sodium (Depakote®) and Lamotrigine (Lamictal®)

Severity: Moderate

Co-administration of valproic acid with lamotrigine [5181] can decrease the elimination of lamotrigine. Valproic acid more than doubles the elimination half-life of lamotrigine in both pediatric and adult patients.[6620] The decrease in apparent clearance of lamotrigine may occur via inhibition of lamotrigine metabolism through competition for liver glucuronidation sites. In any patient receiving valproic acid, lamotrigine must be initiated at a reduced dosage that is less than half the dose used in patients not receiving valproic acid (see Lamotrigine Dosage). In controlled clinical trials, lamotrigine had no appreciable effect on plasma valproic acid concentrations when added to existing valproic acid therapies. If valproic acid therapy is discontinued, lamotrigine doses may need to be adjusted upward. The inhibitory effects of valproic acid on lamotrigine elimination may offset the actions of other anticonvulsants with known hepatic enzyme-inducing properties on lamotrigine clearance.

Valproic acid more than doubles the elimination half-life and steady-state concentration of lamotrigine in both pediatric and adult patients.[7190] The decrease in apparent clearance of lamotrigine may occur via inhibition of lamotrigine metabolism through competition for liver glucuronidation sites. In one study, maximal inhibition of lamotrigine clearance was reached at valproate doses between 250 mg/day and 500 mg/day and did not increase as the valproate dose was further increased. In any patient receiving valproic acid, lamotrigine must be initiated at a reduced dosage that is less than half the dose used in patients not receiving valproic acid. (see Dosage). In controlled clinical trials, lamotrigine had no appreciable effect on plasma valproic acid concentrations when added to existing valproic acid therapies. If valproic acid therapy is discontinued, lamotrigine doses may need to be adjusted upward. The inhibitory effects of valproic acid on lamotrigine elimination may offset the actions of other anticonvulsants with known hepatic enzyme-inducing properties on lamotrigine clearance.[7190]

Cyclobenzaprine (Flexeril®) and Lidocaine (Lidoderm®)

Severity: High

Cyclobenzaprine is structurally similar to tricyclic antidepressants.[5155] Tricyclic antidepressants have reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings).[4951] [5145] [5146] A case of torsade de pointes (TdP) has been reported with cyclobenzaprine, when given in combination with droperidol (also associated with TdP).[5156] Use cyclobenzaprine with caution with drugs which prolong the QT interval. Drugs which have been established to have a causal association with QT prolongation and TdP include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine) [4951] [4952] [5187], Class III antiarrhythmics (amiodarone, bretylium, dofetilide, ibutilide, sotalol) [4951] [4952] [5187], astemizole [140], arsenic trioxide [4951] [4977], bepridil [4951] [4953], cisapride [4951], chloroquine [4951] [4955] [4956] [4967], clarithromycin [4951] [4964], droperidol [3610] [4951] [4963], erythromycin [228] [4951] [4978], grepafloxacin [5149], halofantrine [4951] [4968], haloperidol [42] [336] [4951] [5036], levomethadyl [4951] [5079] [5081] [5146], methadone [4951] [5048] [5049] [5050] [5051], pentamidine [168] [335] [4951] [5149], certain phenothiazines (chlorpromazine [4951], mesoridazine [4951] [5021], and thioridazine [4951] [5022]), pimozide [4951], probucol [5145], sparfloxacin [4951] [4958], and terfenadine [141] [231]. Other agents associated with a lower, but possible risk for QT prolongation and TdP based on varying levels of documentation (see separate drug monographs) include: abarelix [5136], alfuzosin [4988], amoxapine [5145], apomorphine [5392], beta-agonists [4951] [5038] [5047], certain quinolones [5149] [5150] [6579] (ofloxacin [7501], ciprofloxacin [5149] [5496] [5507] [6579], gatifloxacin [5149] [5150] [5152], gemifloxacin [5154], levofloxacin [5149] [5150] [5151], moxifloxacin [5149] [5150] [5153], norfloxacin [6564]), clozapine [5146], dolasetron [5037], flecainide [331] [5484], halogenated anesthetics [5187] [5188] [5486] [5487] [5488], local anesthetics, maprotiline [5145], mefloquine [6617], octreotide [4951], ofloxacin [7501], palonosetron [5148], some phenothiazines (fluphenazine [5145], perphenazine [5145], prochlorperazine [5145], and trifluoperazine [5145]), propafenone [5014] [5146], risperidone [4951] [5144], sertindole [5187], tacrolimus [4049] [4050] [4951], telithromycin [4880], tricyclic antidepressants when given in excessive doses or overdosage [5145] [5146], troleandomycin (based on interactions with macrolides) [5149], vardenafil [4942], or ziprasidone [4959]. This list is not inclusive of all agents that may cause QT interval prolongation. In addition, some of the listed drugs have CYP3A4 inhibitory properties (e.g., amiodarone, erythromycin, clarithromycin, troleandomycin), and could theoretically inhibit the metabolism of cyclobenzaprine. In addition to avoiding concurrent drug interactions (see Drug Interactions), the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).

Cyclobenzaprine (Flexeril®) and Morphine

Severity: Moderate

Cyclobenzaprine (Flexeril®) and Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®)

Severity: Moderate

Loperamide (Imodium®) and Morphine

Severity: Moderate

Additive constipation may be seen with concurrent use of morphine and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract.[6925] Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.[6365] Concurrent use of selected antidiarrheals (e.g., loperamide, diphenoxylate) and morphine can lead to additive CNS depression.

Concurrent use of loperamide and opiate agonists can lead to severe constipation, obstruction/impaction, or paralytic ileus and possibly additive CNS depression.[6855]

Lidocaine (Lidoderm®) and Morphine

Severity: Low

Concomitant use of low-dose local anesthetics (0.125-0.25%) and epidural opiate agonists (e.g., alfentanil, fentanyl, morphine, and sufentanil), may increase analgesia and decrease opiate dosage requirements. The vagal effects and respiratory depression induced by opiate agonists can be increased by local anesthetics.

Concomitant use of local anesthetics and morphine sulfate injection given epidurally, may increase the analgesia and decrease the morphine dosage requirements. NOTE: With the exception of a lidocaine; epinephrine test dose, do not administer local anesthetics within the epidural space before or after injection of morphine sulfate extended-release liposome injection (DepoDur™). The maximum serum concentration of morphine 15 minutes after epidural injection of a test dose (3 ml of lidocaine 1.5% and epinephrine 1:200,000) was similar to the maximum serum concentration of morphine without the local anesthetic (see Administration). Do not administer DepoDur™ any sooner than 15 minutes after a test dose. The effect of other local anesthetics on DepoDur™ has not been evaluated.[5897]

Pramipexole (Mirapex®) and Morphine

Severity: Moderate

Pramipexole (Mirapex®) and Olanzapine (Zyprexa®)

Severity: High

Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa, pergolide, pramipexole, or ropinirole therapy by blocking dopamine receptors in the brain.[5732] Olanzapine may also cause additive sedation with drugs like entacapone [5574], pramipexole [5640], ropinirole [5681] and tolcapone [5578]. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents. Olanzapine should be avoided during therapy for Parkinson's disease unless the benefit of the olanzapine outweighs the risk of decreased therapeutic response to levodopa or other treatments.

Pramipexole is a potent dopamine-receptor agonist.[5640] Dopamine-receptor antagonists, including the antipsychotics (phenothiazines, haloperidol, and thiothixene) should be avoided concurrently because they may antagonize the effects of pramipexole. In general, however, the 'atypical antipsychotics' are less likely to interfere with antiparkinsons treatments than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.[7757]

Pramipexole (Mirapex®) and Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®)

Severity: High

Morphine and Metaxalone (Skelaxin®)

Severity: Moderate

Concomitant administration of metaxalone with barbiturates, ethanol, and other CNS depressants can potentiate the sedative effects of either agent.[6341] [7168] [7198] [7594] Other CNS depressants include anxiolytics, sedatives, and hypnotics; opiate agonists; buprenorphine; butorphanol; nalbuphine; pentazocine; phenothiazines; dronabinol, THC, sedating H1-blockers; tricyclic antidepressants [5290]; tramadol; and the phytomedicinal herbs valerian, Valeriana officinalis or kava kava, Piper methysticum [5559].

Morphine and Olanzapine (Zyprexa®)

Severity: Moderate

Metaxalone (Skelaxin®) and Diphenhydramine (Benadryl®)

Severity: Moderate

Metaxalone (Skelaxin®) and Acetaminophen; Dichloralphenazone; Isometheptene (Amidrine®)

Severity: Moderate

Olanzapine (Zyprexa®) and Cyclobenzaprine (Flexeril®)

Severity: Moderate

Olanzapine (Zyprexa®) and tobacco

Severity: Moderate

Tobacco [5056] smoke contains hydrocarbons that induce hepatic CYP450 microsomal enzymes (e.g., CYP1A1, CYP1A2, CYP2E1). Tobacco smoking causes a substantial (40%) reduction in plasma concentrations of olanzapine.[5517] Although tobacco smokers might require higher doses of olanzapine, dosage modifications are not routinely recommended due to the wide therapeutic index of olanzapine.[5517] Because the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco, the sudden cessation of tobacco smoking may result in a reduced clearance of olanzapine, despite the initiation of a nicotine replacement product. Following one week of abstinence from chronic tobacco smoking, olanzapine clearance may decrease. Patients taking olanzapine should be monitored carefully when changes in smoking status occur. No interaction is expected to directly occur from the use of nicotine replacement products with olanzapine.

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Adverse Reactions

• acne vulgaris (Androderm®)

• acute generalized exanthematous pustulosis (AGEP) (Amidrine®)

• agitation (Benadryl® | Depakote® | Effexor® XR | Celexa® | Zyprexa®)

• akathisia (Effexor® XR | Celexa® | Zyprexa®)

• alopecia (Androderm® | Depakote® | Lipitor® | Chondroitin; Glucosamine)

• amblyopia (Zyprexa®)

• amenorrhea (Lamictal® | Morphine | Androderm® | Celexa®)

• amnesia (Celexa® | Zyprexa®)

• anaphylactic shock (Lidoderm® | Celexa® | Amidrine®)

• anemia (Vitamin C | Lamictal® | Amidrine®)

• angina (Lidoderm® | Fish Oil, Omega-3 Fatty Acids)

• angioedema (Lamictal® | Celexa® | Amidrine® | Zetia®)

• anorexia (Depakote® | Effexor® XR | Celexa® | Amidrine® | Chondroitin; Glucosamine)

• aphasia (Zyprexa®)

• appetite stimulation (Benadryl® | Depakote® | Celexa® | Zyprexa®)

• arachnoiditis (Lidoderm®)

• arthralgia (Lipitor® | Celexa® | Zyprexa® | Zetia®)

• asphyxia (Psyllium)

• ataxia (Benadryl® | Lamictal® | Depakote®)

• back pain (Vitamin C | Lipitor® | Zyprexa® | Fish Oil, Omega-3 Fatty Acids | Zetia®)

• biliary obstruction (Morphine)

• bleeding (Effexor® XR | Vitamin E | Fish Oil, Omega-3 Fatty Acids)

• blepharitis (Zyprexa®)

• bronchospasm (Lidoderm®)

• bullous rash (Lamictal® | Imodium®)

• cardiac arrest (Lidoderm® | Morphine)

• chest pain (unspecified) (Psyllium | Celexa® | Zyprexa® | Zetia®)

• cholecystitis (Zetia®)

• cholelithiasis (Zetia®)

• cholestasis (Lipitor® | Saw Palmetto)

• choreoathetosis (Celexa® | Zyprexa®)

• cirrhosis (Lipitor®)

• coagulopathy (Celexa®)

• contact dermatitis (Benadryl® | Vitamin E | Amidrine®)

• costovertebral pain (Vitamin C)

• cough (Celexa® | Zyprexa® | Zetia®)

• decreased uterine contractility (Lidoderm®)

• dehydration (GlycoLax™)

• dental caries (Vitamin C)

• dental pain (Androderm®)

• depression (Lamictal® | Androderm® | Depakote® | Celexa®)

• diabetes mellitus (Zyprexa®)

• diabetic ketoacidosis (Zyprexa®)

• diaphoresis (Morphine | Depakote® | Effexor® XR | Celexa®)

• diplopia (Lamictal® | Depakote®)

• dysarthria (Benadryl® | Lamictal® | Depakote® | Zyprexa®)

• dysesthesia (Lidoderm®)

• dyskinesia (Benadryl® | Effexor® XR | Zyprexa® | Mirapex®)

• dysmenorrhea (Celexa® | Zyprexa®)

• dysphagia (Zyprexa®)

• dysphoria (Morphine)

• dystonic reaction (Benadryl® | Zyprexa®)

• ecchymosis (Effexor® XR | Fish Oil, Omega-3 Fatty Acids)

• edema (Lidoderm® | Zyprexa® | Amidrine® | Chondroitin; Glucosamine)

• ejaculation dysfunction (Effexor® XR | Celexa®)

• emotional lability (Lamictal® | Zyprexa®)

• encephalopathy (Depakote® | Amidrine®)

• enterocolitis (Vitamin E)

• eosinophilia (Lamictal®)

• epididymitis (Androderm®)

• epiphyseal closure (Androderm®)

• epistaxis (Fish Oil, Omega-3 Fatty Acids)

• eructation (Fish Oil, Omega-3 Fatty Acids)

• erythema (Lamictal® | Lidoderm® | Androderm® | Amidrine®)

• erythema multiforme (Depakote® | Celexa®)

• erythrocytosis (Androderm®)

• euphoria (Morphine | Depakote®)

• exfoliative dermatitis (Amidrine®)

• fecal incontinence (GlycoLax™)

• fecal urgency (GlycoLax™)

• feminization (Androderm®)

• fetal abortion (Celexa®)

• fetal acidosis (Lidoderm®)

• fetal bradycardia (Lidoderm®)

• fever (Lipitor® | Celexa® | Zyprexa® | Amidrine®)

• flatulence (Psyllium | Lipitor® | Celexa® | GlycoLax™)

• flushing (Vitamin C | Morphine)

• galactorrhea (Depakote®)

• GI bleeding (Celexa®)

• GI obstruction (Morphine | Psyllium)

• gingivitis (Lidoderm® | Androderm®)

• gynecomastia (Androderm® | Saw Palmetto)

• halitosis (Fish Oil, Omega-3 Fatty Acids)

• hallucinations (Flexeril® | Benadryl® | Morphine | Depakote® | Mirapex®)

• hemolysis (Vitamin C | Amidrine®)

• hemolytic anemia (Vitamin C | Celexa® | Amidrine® | Skelaxin®)

• hepatic failure (Lipitor®)

• hepatic necrosis (Lipitor® | Celexa® | Amidrine®)

• hepatitis (Androderm® | Lipitor® | Amidrine® | Saw Palmetto)

• hostility (Celexa®)

• hyperalgesia (Morphine)

• hyperammonemia (Depakote®)

• hyperamylasemia (Morphine)

• hypercalcemia (Androderm®)

• hypercholesterolemia (Androderm® | Effexor® XR | Fish Oil, Omega-3 Fatty Acids)

• hyperesthesia (Depakote®)

• hyperglycemia (Depakote® | Zyprexa®)

• hyperoxaluria (Vitamin C)

• hyperprolactinemia (Celexa® | Zyprexa®)

• hypersalivation (Zyprexa®)

• hypertension (Lidoderm® | Morphine | Effexor® XR)

• hypervitaminosis A (Fish Oil, Omega-3 Fatty Acids)

• hypervitaminosis D (Fish Oil, Omega-3 Fatty Acids)

• hyponatremia (Morphine | Effexor® XR | Celexa®)

• hypoprothrombinemia (Amidrine®)

• ileus (Imodium® | Morphine)

• impaired cognition (Benadryl® | Celexa®)

• impotence (Effexor® XR | Celexa® | Saw Palmetto)

• infection (Celexa® | Fish Oil, Omega-3 Fatty Acids | Zetia®)

• injection site reaction (Lidoderm® | Androderm® | Depakote®)

• interstitial nephritis (Amidrine®)

• irritability (Skelaxin®)

• jaundice (Androderm® | Depakote® | Amidrine® | Skelaxin®)

• lacrimation (Zyprexa®)

• lethargy (Depakote®)

• leukopenia (Lamictal® | Depakote® | Amidrine® | Skelaxin®)

• libido decrease (Morphine | Androderm® | Effexor® XR | Celexa® | Zyprexa®)

• libido increase (Androderm®)

• maculopapular rash (Lamictal® | Celexa® | Zyprexa® | Amidrine® | Skelaxin®)

• malaise (Depakote® | Lipitor®)

• mania (Effexor® XR | Celexa®)

• mastalgia (Androderm®)

• menstrual irregularity (Depakote® | Zyprexa®)

• methemoglobinemia (Amidrine®)

• miosis (Morphine)

• myalgia (Lipitor® | Celexa® | Zetia®)

• myasthenia (Lipitor®)

• mydriasis (Benadryl® | Effexor® XR)

• myoclonia (Morphine | Zyprexa®)

• myoglobinuria (Lipitor®)

• myopathy (Lipitor®)

• neonatal abstinence syndrome (Morphine | Effexor® XR | Celexa®)

• neonatal depression (Lidoderm®)

• nephrolithiasis (Vitamin C)

• neuroleptic malignant syndrome (Celexa® | Zyprexa®)

• neuropathic pain (Lidoderm®)

• neutropenia (Zyprexa® | Amidrine®)

• nystagmus (Lamictal® | Depakote®)

• oligomenorrhea (Androderm®)

• orgasm dysfunction (Celexa® | Zyprexa®)

• orthostatic hypotension (Morphine | Celexa® | Zyprexa® | Mirapex®)

• palpitations (Benadryl® | Lidoderm® | Morphine | Chondroitin; Glucosamine)

• pancreatitis (Depakote® | Lipitor® | Celexa® | Zetia®)

• pancytopenia (Amidrine®)

• paresis (Morphine)

• paresthesias (Lidoderm® | Morphine | Depakote® | Celexa® | Zyprexa®)

• peliosis hepatis (Androderm®)

• peripheral edema (Androderm® | Zyprexa®)

• petechiae (Depakote®)

• pharyngitis (Lipitor® | Zyprexa® | Zetia®)

• photosensitivity (Benadryl® | Depakote® | Zyprexa®)

• physiological dependence (Morphine)

• polydipsia (Zyprexa®)

• polyuria (Celexa® | Zyprexa® | Mirapex®)

• priapism (Androderm® | Effexor® XR | Celexa® | Zyprexa®)

• prolonged bleeding time (Depakote® | Fish Oil, Omega-3 Fatty Acids)

• prostatic hypertrophy (Androderm®)

• pseudoparkinsonism (Depakote® | Zyprexa®)

• psychosis (Benadryl®)

• purpura (Amidrine®)

• pyrosis (heartburn) (Chondroitin; Glucosamine)

• QT prolongation (Flexeril® | Effexor® XR | Celexa®)

• renal failure (unspecified) (Celexa® | Amidrine®)

• renal papillary necrosis (Amidrine®)

• renal tubular necrosis (Amidrine®)

• renal tubular obstruction (Vitamin C | Lipitor®)

• respiratory depression (Lidoderm® | Morphine)

• restlessness (Benadryl® | Lidoderm® | Morphine)

• rhabdomyolysis (Effexor® XR | Lipitor® | Celexa® | Zyprexa® | Mirapex®)

• rhinitis (Lamictal® | Celexa® | Zyprexa®)

• rhinorrhea (GlycoLax™)

• secondary malignancy (Androderm®)

• serotonin syndrome (Effexor® XR | Celexa®)

• SIADH (Morphine | Effexor® XR | Celexa®)

• sickle-cell crisis (Vitamin C)

• sinus bradycardia (Lidoderm® | Morphine)

• sinusitis (Lipitor® | Celexa® | Zetia®)

• skin discoloration (Androderm®)

• skin irritation (Androderm® | Vitamin E)

• Stevens-Johnson syndrome (Lamictal® | Depakote®)

• stomatitis (Lidoderm®)

• stroke (Zyprexa®)

• suicidal ideation (Effexor® XR | Celexa® | Zyprexa®)

• syncope (Morphine)

• tardive dyskinesia (Benadryl® | Effexor® XR | Zyprexa®)

• teratogenesis (Depakote®)

• throat irritation (Colace®)

• thrombocytopenia (Lamictal® | Depakote® | Celexa® | Amidrine®)

• thrombosis (Celexa®)

• tolerance (Morphine | Amidrine®)

• torsade de pointes (Celexa®)

• torticollis (Zyprexa®)

• toxic epidermal necrolysis (Lamictal® | Imodium® | Celexa® | Amidrine®)

• urinary incontinence (Lidoderm® | Zyprexa®)

• urinary retention (Benadryl® | Lidoderm® | Morphine | Zyprexa®)

• urticaria (Lidoderm® | Lipitor® | Amidrine® | GlycoLax™)

• vaginitis (Lamictal® | Zyprexa®)

• ventricular fibrillation (Celexa®)

• ventricular tachycardia (Celexa®)

• vesicular rash (Lamictal® | Zyprexa®)

• virilization (Androderm®)

• weight gain (Androderm® | Depakote® | Celexa® | Zyprexa® | Fish Oil, Omega-3 Fatty Acids)

• weight loss (Depakote® | Effexor® XR | Celexa®)

• withdrawal (Morphine | Effexor® XR | Celexa®)

• xerophthalmia (Benadryl®)

• xerosis (Zyprexa®)

• yawning (Celexa®)

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Indication Alerts

Drugs that can be used to treat current conditions:

• Amidrine® can be used to treat headache

• Androderm® can be used to treat hypogonadism

• Benadryl® can be used to treat allergic rhinitis, and Parkinson's disease

• Celexa® can be used to treat depression

• Chondroitin; Glucosamine can be used to treat osteoarthritis

• Colace® can be used to treat constipation

• Depakote® can be used to treat bipolar disorder

• Effexor® XR can be used to treat depression, headache, and neuropathic pain

• Fish Oil, Omega-3 Fatty Acids can be used to treat nutritional supplementation

• Flexeril® can be used to treat muscle spasm

• GlycoLax™ can be used to treat constipation

• Imodium® can be used to treat diarrhea

• Lamictal® can be used to treat bipolar disorder

• Lidoderm® can be used to treat headache, local anesthesia, neuropathic pain, and severe pain

• Lipitor® can be used to treat hypercholesterolemia

• Mirapex® can be used to treat Parkinson's disease

• Morphine can be used to treat bone pain, diarrhea, headache, and severe pain

• Psyllium can be used to treat constipation, diarrhea, and hypercholesterolemia

• Saw Palmetto can be used to treat benign prostatic hyperplasia (BPH)

• Skelaxin® can be used to treat muscle spasm

• Vitamin C can be used to treat nutritional supplementation

• Vitamin E can be used to treat nutritional supplementation

• Zetia® can be used to treat hypercholesterolemia

• Zyprexa® can be used to treat bipolar disorder

Conditions not currently being treated:

• renal impairment

________________________________________________________________________________

Precautions

Precaution: Amidrine® in renal impairment

Acetaminophen; dichloralphenazone; isometheptene should be prescribed cautiously in certain high risk patients such as elderly or debilitated patients, patients with cardiac disease (e.g., angina, cardiac arrhythmias, hypertension, or immediately following a myocardial infarction), diabetes mellitus, glaucoma, severe hepatic disease (e.g., alcoholic hepatic disease, viral hepatitis or alcoholism), peptic ulcer disease, pulmonary disease, severe renal disease/renal impairment, or thyroid disease. Acetaminophen should not be used in patients who consume 3 or more alcoholic beverages per day. Acetaminophen should be used cautiously in patients with asthma who also have salicylate hypersensitivity. Of 50 patients with aspirin-sensitive asthma, 17 had either a naso-ocular or bronchospastic reaction after ingestion of either 1000 mg or 1500 mg of acetaminophen. The magnitude of FEV1 decline after a mean aspirin dose of 47 mg was similar to the decline seen after a mean acetaminophen dose of 1227 mg. The lower the aspirin provocative dose, the more likely patients were to cross-react to acetaminophen. For example, 5 of 6 patients with aspirin-induced bronchospasm after a dose of 30 mg or less had cross-reactivity to acetaminophen whereas no patients had cross-reactivity when the provocative aspirin dose was at least 150 mg. The acetaminophen challenges were performed before any aspirin challenges and all patients had a measured FEV1 of at least 70% of predicted or best previously recorded value, an absolute value greater than 1.5 liters, and a fall of less than 15% in FEV1 from morning baseline during placebo challenges.[1112]

Precaution: Celexa® in bipolar disorder

Citalopram is not FDA-approved for the treatment of depression in pediatric patients. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. Patients with suicidal ideation, including both adult and pediatric patients, should be closely supervised, whether or not they are taking an antidepressant. In addition, all antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms (see Adverse Events), worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that citalopram is not approved for use in treating bipolar depression.

Precaution: Celexa® in renal impairment

Excretion of unchanged citalopram in the urine is a minor route of elimination. However, citalopram should be used with caution in patients with severe renal impairment (i.e., CrCl < 20 ml/min) until this population has been evaluated during chronic treatment with citalopram. There is no information on the use of citalopram in patients with chronic renal failure who receive hemodialysis.

Precaution: Chondroitin; Glucosamine in renal impairment

Chondroitin and glucosamine are both excreted in the urine to some degree. Glucosamine is metabolized in the liver. Studies of chondroitin; glucosamine do not exist for patients with renal disease or hepatic disease; caution is warranted with supplementation in these individuals. Patients with renal impairment or renal failure should avoid chondroitin; glucosamine products that are available in combination with minerals that may accumulate in renal impairment.

Precaution: Depakote® in renal impairment

Valproic acid should be used with caution in patients with renal disease, such as severe renal impairment or renal failure, because uremia can cause increased free fraction of drug, resulting in possible toxicity. Also, unbound valproic acid level (i.e., the free-fraction) in the blood may be cleared more rapidly than the protein-bound drug; close monitoring of valproic acid serum concentrations may be warranted in those with renal impairment to ensure adequate dosage and to limit toxicity.

Precaution: Effexor® XR in renal impairment

Venlafaxine should be used with caution in patients with renal impairment or renal failure because clearance is reduced. Patients with hepatic impairment have an increase in plasma concentrations of venlafaxine compared to patients without hepatic disease. Thus, this drug should be used with caution in patients with hepatic impairment. Reduced dosages of venlafaxine may be necessary in these patient populations (see Dosage).

Precaution: Fish Oil, Omega-3 Fatty Acids in bipolar disorder

Limited data are available on use of fish oil, omega-3 fatty acid supplements in a variety of health conditions, including asthma (or other pulmonary disease), cardiac disease (including atherosclerosis, hypertension, myocardial infarction), diabetes mellitus, inflammatory bowel disease, migraine, psychiatric illness (like bipolar disorder or schizophrenia) various types of nephropathy (renal disease), rheumatoid arthritis, systemic lupus erythematosus (SLE), and many others. Fish oil products are not intended to diagnose, treat, cure, or prevent any disease. Safety and efficacy for many of these conditions is still not established. Consumers should be encouraged to consult their health care provider prior to the administration of fish oil capsules for the adjunctive treatment of these conditions. Other prescribed therapies should be continued as directed by their health care provider.

Precaution: Fish Oil, Omega-3 Fatty Acids in hypercholesterolemia

Because fish oil, omega-3 fatty acids may increase LDL or total serum cholesterol, they should be used cautiously in patients with hypercholesterolemia or mixed dyslipidemias. As with any lipid-regulating product, LDL-C levels should be monitored periodically. Additionally, clinicians should be aware that some fish oil supplements increase the daily calorie intake and hence may induce weight gain, which may be detrimental to some patients with cardiovascular risk factors, like obesity.

Precaution: Flexeril® in depression

Because of the drug's chemical similarity to tricyclic antidepressants (TCAs), use cyclobenzaprine with caution in patients being treated for psychological illness. Cyclobenzaprine is not an effective treatment for depression. Cyclobenzaprine is contraindicated for concomitant use in patients receiving MAO inhibitor therapy (see Drug Interactions). It is unclear if cyclobenzaprine, like the TCAs, can transform depression into mania or hypomania in predisposed individuals (e.g., some patients with bipolar disorder). Also use cyclobenzaprine with caution in patients with psychotic disorders (e.g., schizophrenia).

Precaution: Lamictal® in renal impairment

Lamotrigine should be used with caution in patients with severe renal impairment or renal failure. Initial doses of lamotrigine should be based on the patient's current antiepileptic drug regimen. Reduced maintenance doses of lamotrigine may be effective in maintaining seizure control. In one study of patients with chronic renal failure, the mean plasma half-life of lamotrigine was 42.9 hours, compared to 26.2 hours in healthy volunteers. During hemodialysis sessions the mean plasma half-life was 13 hours, and 57.4 hours between hemodialysis (manufacturer's data).

Precaution: Lipitor® in renal impairment

Other HMG-CoA reductase inhibitors have been associated with toxicity to the skeletal muscle system. Myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values > 10 times upper limit of normal (ULN), should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Any evidence of myalgia, muscle weakness, or elevated CPK values may indicate myopathy, particularly if symptoms include fever or malaise. Clinicians should note that rhabdomyolysis and renal failure have been associated with HMG-CoA reductase inhibitor therapy. The risk of developing myopathy appears to be increased when HMG-CoA reductase inhibitors are used in combination with other drugs (see Drug Interactions). Atorvastatin should be discontinued immediately in any patient who develops myopathy or elevations in CPK. In addition, atorvastatin may be contraindicated in conditions that can cause decreased renal perfusion because renal failure is possible if atorvastatin-induced rhabdomyolysis occurs. Predisposing conditions include renal disease or renal impairment, hypotension, acute infection, endocrine disease, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Atorvastatin should be used with caution in organ transplant patients receiving immunosuppressant therapy such as cyclosporine because of an increased risk of rhabdomyolysis and renal failure (see Drug Interactions). Renal disease has no influence on atorvastatin plasma concentrations or LDL cholesterol reductions; dosage adjustments are not needed in patients with renal impairment.

Precaution: Mirapex® in renal impairment

Urinary excretion is the major route of pramipexole elimination, with 90% of a dose excreted unchanged in urine. Clearance of pramipexole is 60-70% lower in patients with moderate-severe renal impairment (CrCl <= 40 ml/min) than in patients with normal renal function. Dosages should be adjusted in patients with a CrCl <= 60 ml/min (see Dosage). Use of pramipexole has not been adequately studied in patients with a CrCl <= 15 ml/min or in patients undergoing hemodialysis (a negligible amount of pramipexole is removed by dialysis). In general, pramipexole should be used with caution in patients with renal impairment.

Precaution: Morphine in constipation

Morphine is contraindicated in patients with paralytic ileus. Due to the effects of opiate agonists on the gastrointestinal tract, morphine should be used cautiously in patients with GI disease including GI obstruction, ulcerative colitis, or pre-existing constipation. Patients with ulcerative colitis (UC) or other inflammatory bowel disease may be more sensitive to the constipating effects of opiate agonists. Opiate agonists may obscure the diagnosis or clinical course in patients with an acute abdomen. Although opiate agonists are not desirable for use in patients with diarrhea secondary to poisoning or infectious diarrhea, antimotility agents have been used successfully in these patients. If possible, opiate agonists should not be given until the toxic substance has been eliminated.

Precaution: Morphine in diarrhea

Precaution: Morphine in renal impairment

Morphine and other opiate agonists can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with bladder obstruction, prostatic hypertrophy, urethral stricture, pelvic malignancy, or renal disease. Drug accumulation or prolonged duration of action can occur in patients with renal impairment or hepatic disease. In acute situations, patients require close monitoring to avoid excessive toxicity. Patients with chronic liver or renal disease may require less frequent dosing intervals.

Precaution: Morphine in constipation

Precaution: Morphine in diarrhea

Precaution: Morphine in renal impairment

Precaution: Skelaxin® in renal impairment

with significant renal impairment or hepatic dysfunction (hepatic disease). The drug is also contraindicated in patients with a history of drug-induced hemolytic anemia or other types of anemia.

Precaution: Zyprexa® in Parkinson's disease

Olanzapine is less likely than the typical antipsychotics to cause extrapyramidal side effects; atypical antipsychotics are typically preferred for the treatment of Parkinson's related dementia when such treatment is needed. However, all antipsychotics should be used with caution in those patients with Parkinson's disease because of possible aggravation of EPS due to dopamine-receptor blockade. No studies are available to evaluate the incidence of stroke when olanzapine is used to treat Parkinson's-related dementia; although extreme caution is advised.

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Allergy Alerts

No warnings noted

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Therapeutic Duplications

• Amidrine® and Benadryl® are Anxiolytics.

• Amidrine® and Benadryl® are Sedatives.

• Amidrine® and Benadryl® are and Hypnotics.

• Celexa® and Effexor® XR are Antidepressants.

• Chondroitin; Glucosamine, Fish Oil, Omega-3 Fatty Acids, and Saw Palmetto are Nutraceuticals.

• Colace®, GlycoLax™, and Psyllium are Laxatives and Stool Softeners.

• Depakote® and Lamictal® are Anticonvulsants.

• Depakote® and Lamictal® are Antimanics.

• Fish Oil, Omega-3 Fatty Acids, Lipitor®, and Zetia® are Antilipemics.

• Flexeril® and Skelaxin® are Skeletal Muscle Relaxants.

• GlycoLax™ and Psyllium are Laxatives.

• Vitamin C and Vitamin E are Vitamins.

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References

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