Disclaimer

*Results may vary. The information in this site is NOT to be construed as medical advice. Cirrhosis of the liver is a serious condition and if you have it, you should see a doctor. I am not a doctor and am not able to dispense medical advice. My husband saw a doctor (many of them) and they were able to do things for him that I could not. However, they were unable to recommend alternative treatments that were VERY beneficial to my husband, so I am providing some of that information here. My husband and I tried all of these alternative therapies at our own risk, and if you try them you will be doing the same. At your own risk. No promises are made in this blog. I am not saying there is a cure for cirrhosis or any other condition. However, I believe most people can get well, like my husband did. My husband is alive, happy, productive, functional and has his energy back. He no longer has to take medications and he no longer worries about having to go on disability or getting a $577,000 liver transplant. Cirrhosis is a serious condition. He is currently in the fibrosis stage (Stage 2 liver disease), which is still serious. I cannot guarantee you will have the same results. I just want you to know about what worked well for my husband. I hope you will share what you learned with others, and share your story with us as well. This blog was made for YOU! Thanks for visiting!

Monday, July 4, 2016

What You MUST Know about getting Dental Work / Prescription Meds if you've been diagnosed with Liver Disease or Cirrhosis


Because I know how common it is for people to develop dental problems, after you are diagnosed with liver disease or cirrhosis, I thought it was worth making this post, to tell you about what happened to my husband recently when he started taking 3 prescriptions given to him by his dentist. What I have concluded is that antibiotics (particularly when mixed with pain killers) can be VERY dangerous for someone with any degree of liver disease and they can make a person very sick!!! And DO NOT expect your dentist, or pharmacist, to ask you if you have any degree of fibrosis... they will not!

My husband had two teeth pulled recently (and unfortunately those weren't the first, since he was diagnosed with cirrhosis).  Once your liver becomes cirrhotic, your body is unable to process calcium properly, and you will be subjected to extreme bone loss, and your teeth will probably start to fall out!  It will be especially bad if you are taking proton pump inhibitors.

My husband has had implants put in. The amount of money he's spent on getting JUST A FEW teeth fixed is equivalent to what it would have cost to buy a professional grade PEMF machine, a detox water machine, and a few years' worth of supplements!  I recently talked to a woman who told me her boyfriend (who got cirrhosis the same way Jake did) spent $65,000.00 on having all his teeth replaced!

So please, people... do whatever you can to prevent cirrhosis, before it even starts. The amount of money you would spend, fixing the problems, is FAR more than you would spend to prevent it (AND YOU WILL ENJOY YOUR LIFE WAY MORE).

For anyone who has cirrhosis via alcohol (like my husband did), please, quit drinking alcohol ASAP.  Get help to deal with the emotions and/or whatever you are suppressing that is making you want to drink. Get into either a rehab facility or start listening to motivational autiotapes and books to turn your life around. Join a fitness program like 24 hour fitness, or Phoenix Multisport if you have one in your area.

OK sorry I am getting off track but you know certain things I just cannot stress enough!

Anyway, when I got home, I looked up all those medications his dentist gave my husband, and sure enough...  although liver failure is not necessarily common when you take these medications, they do list it on the websites for a reason.

This is all one more reminder to me that  
 YOU CANNOT RELY ON DOCTORS OR DENTISTS OR PHARMACISTS TO VERBALLY TELL YOU THAT A MEDICATION COULD BE DOWNRIGHT DANGEROUS FOR YOU, OR IF IT WILL CAUSE PROBLEMS FOR YOUR LIVER. 
YOU HAVE TO LOOK IT UP YOURSELF!!!


Please have a look at this video if you get a chance.



You would think that the pharmacist at Costco would have been able to look at his history of medications and say, "Hmmm... it looks like you were diagnosed with cirrhosis at some point, and could still have some form of liver disease.... are you sure you want to be taking this?"  Sorry...even though pharmacists typically make about $82,000.00 per year, they are just not required to go that far.  I was actually the person who picked up all these medications for my husband, and the pharmacist read all the instructions to me (it took about 2 minutes for her to go over everything)... but she never mentioned anything about possible damage to the liver.

I suppose I can understand this, since they see soooo many sick people who have so many health problems, if they made everyone stand in line to listen to a long speech about every one of the potential side effects of every medication...that line at the pharmacy would be soo long, people would be more annoyed than they already are. I already get impatient when I have 2 or 3 people in front of me and have to wait more than 5 minutes in the pharmacy line!

UPDATE 11/15/16: I have been meaning to tell you guys... about a month ago, a man told me that his pharmacist - who was his long time pharmacist and friend, actually told him, I could lose my job over this, but I have to tell you... I don't think you should take this antibiotic the doctor prescribed for you... because you have cirrhosis, it could kill you.  I... kid... you... not.  There seems to be soooo much that doctors and dentists and pharmacists do NOT tell the majority of us! When I heard that, I wanted to shout, I KNEW IT!!! Like when a woman from the Czech republic told me her husband developed encephalopathy from drinking MILK (not even meat). There is just sooooo much that we will NOT learn from our doctors and the people who are supposed to be authorities on this subject. We're left to figure it all out on our own!


The dentist wrote 3 prescriptions for him, for the following meds (you can see their side effects further down the page):

Amoxicillin (500 mg) 
Metronidazole (250 mg)
Hydrocodone / Acetaminophen (325)

Note: it's a little confusing that they don't say how many milligrams of Hydrocodone my husband was prescribed...on the bottle, it just says Hydrocodone / Acetaminophen, without showing the exact amount of each. After finding the information about how the combination of Hydrocodone / Acetaminophen is very bad for the liver (when the acetaminophen is above 325 mg), I assume that the bottle says "Hydrocodone / Acetaminophen (325)" because it's 325 mg of Acetaminophen... but what about the amount of Hydrocodone? How come they don't put the mg of that on the bottle? I guess I have to go find that paper that came with the prescription, or go back to Costco and ask the pharmacist about it... let's just say "it's on the to do list".... and that list is really long.

I feel kind of stupid for just now realizing, oh yeah, duh... Acetaminophen is the same thing as Tylenol, which I've heard is bad for the liver, but somehow when you see commercials you whole life, showing all these healthy, happy people (aka ACTORS) who are taking it and they seem just fine... it has a way of making you forget how serious the side effects can be, if a person has a damaged liver.

Today we went to a 4th of July event, and while we were there, I could see my husband kind of grabbing at his back, like he was having some back pain. When we drove home, I asked him what was going on with that, and he said he back had been bothering him a lot lately, and said he suspected it could be related to the prescription meds he had been taking after he had the dental work.

UPDATE: I have to add, a few days later he showed me he was even developing some swelling in his legs and a few weeks later, he started getting some fluid in his abdomen!!!! This is serious, people. Please believe me when I say, those prescrition drugs - especially when they are all mixed together - can be DANGEROUS.... luckily his swelling seems to be going down, but it really had me scared for a while! He started using a different setting on the water machine and I am so grateful for that machine because it actually seemed to work and he said he felt a lot better! I cannot advise anyone else to use that setting, I am just saying this is what he did.

When we got home, I asked him if I could see all his prescription bottles, looked everything up, and emailed him what I found.... and decided to make a post about it for the rest of you guys who are going through the same thing.  You can see what I found, below. And yeah, sure enough... those medications are not exactly good for the liver!  Each of these meds, by themselves, may not be enough to cause acute liver damage, but for a person in stage 2 liver disease, who is taking THREE medications which are not good for the liver, all at once... that's not a good thing!

I am not really worried about my husband because we are very lucky to have a water machine and a PEMF machine at home, and we have learned through trial and error what supplements are the most helpful. So I am confident that whatever problems he is having with his liver, can be reversed fairly soon. 

I should note that my husband has barely used his BEMER machine this whole last week (and he's been using it every day since we got it in April). And he's used PEMF pretty regularly since the summer of 2014.

But my sister was in town, traveling with a friend of hers, and we usually keep the PEMF machine in the guest room. Because my sister and her friend were staying in the guest room, I moved the PEMF mat into the living room, setting it up on a zero gravity chair so my hubby could sit on it there. But my sister was often working in the living room (while her friend was working in the guest room), and my hubby has this thing where, he just likes to be alone, and very "zen" when he sits on the mat to get a treatment. He's all about routine, and if he's used to doing things a certain way, and then everything changes... he gets a little bent out of shape.  I offered to set up the Bemer in the TV room (where he spends most of his downtime), but he felt it would take up too much space, and he was being a little stubborn and just opted to skip most of his treatments for the last week.

Anyway, my sister and her friend just left, and now my hubby can get back to his Zen Routine, use the Bemer machine again, and hopefully he will be back on track within a few days. Costco is closed but I want to make him some green juice and carrot juice to help him detox his liver from all those meds. He will be drinking more detox water now that he knows the facts about those meds his dentist gave him!! 

If you are planning to have dental work done, and have had cirrhosis or liver disease in the past or present, please have a good look at the details on these medications. I'm not saying you shouldn't take them, but you should at least be aware of the potential side effects. If my husband had known this stuff, he said he would have skipped the pain meds and just dealt with it, and I would have encouraged him to do probiotics instead of antibiotics.

Hope this helps!

Ellie

OVERVIEW
Amoxicillin

Amoxicillin is considered a third generation or aminopenicillin and is one of the most commonly prescribed antibiotics.  Amoxicillin and other aminopenicillins have been linked with idiosyncratic liver injury, but only rarely and in isolated case reports.


Background

Amoxicillin (a mox' i sil' in) is an orally available aminopenicillin that has been available in the United States since 1980, for which currently more than 50 million prescriptions are filled yearly.  Amoxicillin is used to treat mild to moderate infections caused by susceptible agents, such as (but not limited to) Escherichia coli, Hemophilis influenzae, Listeria monocytogenesis, Neisseria gonorrhoeae, Proteus mirabilis, Salmonella, Shigella, Staphylococcus aureus (non-penicillinase producing), Staphyloccocus epidermidis, and Streptococcus pneumoniae.  Amoxicillin is available in multiple generic formulations as tablets or capsules of 250, 500 and 875 mg and is usually given in doses of 250 to 850 mg every 8 hours for 7 to 14 days.  Pediatric formulations in liquid suspension and chewable tablets are also available.


Hepatotoxicity

Rare instances of idiosyncratic liver injury have been reported in persons receiving the aminopenicillins including amoxicillin.  Cases are characterized by a short latency period of a few days to as long as two weeks.  The onset of liver injury can occur after the antibiotic is stopped.  The serum enzyme pattern associated with aminopenicillin liver injury has included a hepatocellular pattern with marked elevations in ALT and AST, and minimal elevations in alkaline phosphatase and rapid recovery after withdrawal.  In addition, cholestatic forms of hepatic injury with marked alkaline phosphatase elevations (as also seen with penicillin-induced liver injury) have also been described, some of which have been associated with prolonged cholestasis (Case 1).  The onset of hepatic injury may be accompanied by signs or symptoms of hypersensitivity such as eosinophilia, rash and arthralgias, and in some cases is accompanied by toxic epidermal necrolysis or Stevens Johnson syndrome. 

 

Likelihood score: B (highly likely but rare cause of clinically apparent liver injury).


 

Much more common than liver injury from amoxicillin alone is the typically cholestatic hepatitis that occurs after treatment with the combination of amoxicillin and clavulanate.  Indeed, this combination is currently the most common cause of idiosyncratic acute liver injury in the United States, Europe and Australia.  The injury, however, is usually attributed to the clavulanate rather than amoxicillin.  The clinical features are similar but perhaps not completely the same.  In cases of liver injury seeming due to amoxicillin, an extra effort should be made to make sure that it was not amoxicillin/clavulanate [Augmentin] that was taken.


Mechanism of Injury

The cause of the liver injury associated with amoxicillin use is probably hypersensitivity or allergy.  Recurrence with reexposure is highly likely, but intentional rechallenge has not been described.


Outcome and Management

In the few cases that have been described, the majority of patients have recovered, although recovery has been slow in some cholestatic instances (2 to 6 months).  Rare instances of acute liver failure and several cases of vanishing bile duct syndrome have been reported with aminopenicillin induced liver injury.  Corticosteroids have often been used to treat the allergic manifestations of penicillin related immunoallergic hepatitis; while corticosteroid therapy may improve fever and rash promptly, their efficacy in ameliorating the accompanying liver disease has not been shown.  Instances of recurrence of liver injury with unintentional reexposure to aminopenicillins and recurrence with exposure to cephalosporins have been reported.  Patients with aminopenicillin induced hepatitis should avoid reexposure to other penicillins and should take cephalosporins with caution.

 

References to the hepatotoxicity and safety of amoxicillin are given in the Overview section on the aminopenicillins.


Drug Class:  Antiinfective AgentsAminopenicillins

 

Other Drugs in the Subclass, Aminopenicillins:  Amoxicillin/ClavulanateAmpicillinAmpicillin-Sulbactam, Bacampicillin, Pivampicillin


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CASE REPORT
Amoxicillin

Case 1. Cholestatic hepatitis due to amoxicillin therapy.
[Modified from Bolzan H, Spatola J, Castelletto R, Curciarello J. Cholestasis intrahepatica inducida por amoxicilina sola. Gastroenterol Hepatol 2000; 23: 237-9]

 

A 24 year old woman developed anorexia and weakness followed by dark urine and itching 5 days into a 10 day course of amoxicillin for pharyngitis and fever.  Within days of finishing the 10 day course, a friend told her that she looked jaundiced.  Ten days after stopping the antibiotic, she sought medical care for continuing jaundice and pruritus.  Serum ALT, AST and alkaline phosphatase were only modestly elevated, but total serum bilirubin was 10.5 mg/dL with a direct fraction of 8.0 mg/dL.  There was no eosinophilia, rash or fever.  Tests for viral hepatitis and autoantibodies were negative.  An ultrasound of the liver was normal.  Her jaundice deepened, and she underwent endoscopic retrograde pancreato-cholangography (ERCP) which was also normal.  A liver biopsy showed intrahepatic cholestasis, mild portal inflammation, but little hepatocellular injury, compatible with a resolving cholestatic hepatitis secondary to a medication.  She had taken no other medications, herbals or over-the-counter products and had no previous history of liver disease or alcohol abuse.


Key Points

Medication:Amoxicillin (1500 mg daily for 10 days)
Pattern:Cholestatic (R=1.2)
Severity:3+ (jaundice and hospitalization)
Latency:Five days
Recovery:Two months
Other medications:None





OVERVIEW
Metronidazole

Introduction

Metronidazole is a nitroimidazole derivative bactericidal agent widely used in the treatment of many anaerobic and certain protozoan and parasitic infections.  Metronidazole has been linked to rare instances of acute, clinically apparent liver injury.


Background

Metronidazole (met" roe nid' a zole) is a nitroimidazole antibiotic that is activated by reduction of its nitro group by susceptible organisms.  The activated form of metronidazole is a highly reactive radical anion which targets and damages large protein molecules and DNA.  Mammalian cells do not ordinarily activate metronidazole, which accounts for its lack of toxicity in humans.  Metronidazole was approved for use in the United States in 1963 and currently several million prescriptions are filled yearly.  Metronidazole is indicated for treatment and prophylaxis of infections with susceptible anaerobic bacteria and protozoa.  The recommended dosage is 500 to 750 mg taken orally three times daily for 5 to 10 days.  Metronidazole is available alone in tablets of 250, 375, 500 and 750 mg as well as in combination with other medications, in multiple generic formulations and under several brand names including Flagyl, Metryl, Noritate, Pylera and Helida.  Other formulations include injectable solutions, extended release tablets, suppositories, and topical creams.  The most common side effects include metallic taste, nausea, vomiting, abdominal discomfort and diarrhea.


Hepatotoxicity

Despite the wide use of metronidazole, only rare cases of hepatotoxicity have been reported, and metronidazole is not listed among causes of drug induced liver injury and acute liver failure in large case series.  High doses of metronidazole given parenterally or in an overdose can cause elevations in serum aminotransferase levels, but these are usually self-limited and minimally symptomatic (Case 1).  Acute, clinically apparent liver injury from metronidazole is rare.  Ornidazole, another synthetic nitroimidazole that was available in Europe, was implicated in several cases of drug induced liver injury, with a latency of a few days or weeks and a hepatocellular pattern of injury.  Metronidazole has been associated with a similar acute hepatitis-like syndrome with a short incubation period, but much more rarely.  Fever, rash and eosinophilia are uncommon as are autoimmune features.  A fatal recurrence of acute liver injury after reexposure to metronidazole has been published (Case 2).  Strikingly, multiple instances of metronidazole hepatoxicity have been reported in the rare genetic disease, Cockayne syndrome in which there is an absence or deficiency in an important DNA repair enyzme responsible for nucleotide excision repair.  The cases were marked by a short latency (1 to 7 days) to onset of jaundice, a hepatocellular pattern of enzyme elevations and severe course with a high mortality rate.


Mechanism of Injury

The cause of acute liver injury due to metronidazole is probably immunoallergic, given the short latency period and recurrence with rechallenge.  However, the frequency  of severe hepatotoxicity in children with Cockayne syndrome suggests a direct toxic effect, probably involving breaks in double stranded DNA.


Outcome and Management

The liver injury from metronidazole is rare, but can result in liver failure and death.  In typical cases, recovery is expected in 1 to 3 months.  Rechallenge results in prompt recurrence and should be avoided.


Drug Class:  Antiinfective Agents; Gastrointestinal Agents

 

Other Drugs in the Subclass, Nitroimidazoles:  Tinidazole

 

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Before taking this medicine

You should not use this medication if you are allergic to metronidazole, or if you are in the first trimester of pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment.
Before taking metronidazole, tell your doctor if you are allergic to any drugs, or if you have:
  • liver disease;
  • a stomach or intestinal disease such as Crohn's disease;
  • a blood cell disorder such as anemia (lack of red blood cells) or leukopenia (lack of white blood cells);
  • epilepsy or other seizure disorder; or
  • nerve disorders.
If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.
Metronidazole can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.



CASE REPORTS 
Metronidazole

Case 1.  Elevations in serum aminotransferase levels during intravenous metronidazole therapy.

[Modified from:  Appleby DH, Vogtland HD. Suspected metronidazole hepatotoxicity. Clin Pharm 1983; 2: 373-4. PubMed Citation]

A 58 year old man underwent prostate biopsy and cystoscopy and 32 hours later developed fever and was admitted for treatment of suspected urosepsis.  After a combination of cephalosporin and tobramycin failed to affect his course, intravenous metronidazole (500 mg every 6 hours) was added.  He had rapid clinical improvement, but then complained of abdominal pain, nausea, headache, and a metallic taste.  Metronidazole was stopped after 5 days, and he was switched on oral cefaclor.  At the same time, serum ALT and alkaline phosphatase levels were found to be elevated.  Physical exam showed slight hepatomegaly without jaundice.  Hepatitis B serology was negative.  Over the following week, the patient recovered symptomatically and was discharged home.  All laboratory tests were normal 4 weeks after stopping metronidazole.


Key Points

Medication:Metronidazole, 500 mg iv every 6 hours for 5 days
Pattern:Hepatocellular (R=10)
Severity:1+ (ALT elevations without jaundice)
Latency:5 days
Recovery:24 days after stopping
Other medications:Cefaclor, tobramycin

Laboratory Values

Time After StartingTime After StoppingALT (U/L)Alk P (U/L)Bilirubin (mg/dL)Other
PrePre
65
Prostate biopsy, cystoscopy





Fever 104 oF: cefapirin, tobramycin
0
Start iv metronidazoleContinued fever
5 days0Stop metronidazoleStarted cefaclor
6 days1 day7202000.4GGT 459
7 days2 days
2380.5
9 days4 days4641910.9
10 days5 days319


2 weeks9 days16771
Discharged
4 weeks24 days42800.3
Normal Values<42<115<1.2

Comment

The serum enzyme elevations were compatible with mild metronidazole hepatotoxicity, given the short latency period and rapid recovery after stopping.  The rapid onset and rapid recovery after high doses of intravenous metronidazole suggest direct hepatic injury.  However, idiosyncratic cases are also marked by short latency period and rechallenge, even with oral metronidazole should be avoided.


Case 2.  Acute hepatocellular injury due to metronidazole with fatal recurrence on reexposure.

[Modified from:  Björnsson E, Nordlinder H, Olsson R. Metronidazol as a probable cause of severe liver injury. Hepatogastroenterology 2002; 49: 252-4. PubMed Citation]

A 24 year old woman was treated with metronidazole for Clostridium difficile infection after a course of penicillin for a tooth abscess.  Her diarrhea improved, but a few days later she developed nausea and vomiting followed by jaundice.  Her past medical history included asthma and frequent upper respiratory infections.  Laboratory tests showed total bilirubin of 7.9 mg/dL with marked elevations in serum aminotransferase levels, but modest increase in alkaline phosphatase (Table).  Tests for hepatitis A, B ad C and for autoantibodies were negative.  An ultrasound showed no evidence of biliary obstruction.  Metronidazole was discontinued and she began to improve, but her recovery was slow and symptoms persisted for at least two months and laboratory tests did not return to normal for at least nine months.  Two years later, she was treated for bacterial vaginitis with metronidazole and tetracycline and one week later developed nausea, vomiting and jaundice.  Serum bilirubin was 12.2 mg/dL, ALT and AST were more than 100 fold elevated, and prothrombin index was <9%.  She was transferred to a liver transplant center where she developed progressive hepatic coma.  Tests for hepatitis A, B and C were again negative.  She underwent liver transplantation, but died in the perioperative period.  Explant showed massive hepatic necrosis and cholestasis.


Key Points

Medication:Metronidazole (dose and duration not given)
Pattern:Hepatocellular (R=62)
Severity:3+ initially (jaundice and hospitalization)
5+ on reexposure (liver transplantation, death)
Latency:~5-10 days
Recovery:10 months after initial exposure
Other medications:Oral tetracycline

Laboratory Values

Time After StartingTime After StoppingALT* (U/L)Alk P* (U/L)Bilirubin *(mg/dL)Other
0
Metronidazole given for C difficile
~10 days052826067.9
15 days5 days300050020.1
1 mo1 mo10445010.5
2.5 mos2.5 mos1024921.0
9 mos9 mos84<3001.0

26 mosMetronidazole given for bacterial vaginitis
~7 days01110481012.2Protime index < 9%
~10 days~3 days

20.5Liver transplant, post-operative death
Normal Values<42<300<1.2

*Values estimated from Figure 1. Bilirubin results converted from mol to mg/dL (17.1) and enzyme results converted from kat to U/L (0.01667).


Comment

Severe acute hepatocellular injury from a short course of metronidazole with slow recovery, followed by tragic rapid and fatal recurrence on reexposure.


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PRODUCT INFORMATION
Metronidazole

REPRESENTATIVE TRADE NAMESMetronidazole – Generic, Flagyl®


DRUG CLASSAntiinfective Agents



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DRUG RECORD


HYDROCODONE

OVERVIEW
Hydrocodone

Introduction

Hydrocodone is a semisynthetic, moderately potent, orally available opioid that, in combination with acetaminophen, is widely used for treatment of acute or chronic pain, and in combination with antihistamines or anticholinergics used to treat cough.  Hydrocodone by itself has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury, but the combination with acetaminophen has been linked to many cases of acute liver failure due to unintentional overdose with acetaminophen.


Background

Hydrocodone (hye” droe koe’ done) is a semisynthetic derivative of codeine or thebaine, natural alkaloids derived from the resin of poppy seeds (Papaver somniferum).  It is well absorbed orally and has moderate opiate activity (approximately 6 times that of codeine), acting an agonist of the µ opiate receptor.  The combination of hydrocodone with acetaminophen is effective in ameliorating moderate-to-moderately severe pain and is widely used for temporary as well as chronic management of pain states.  The combination of hydrocodone with acetaminophen or other products helps to prevent its recreational use and administration by injection.  Hydrocodone has been in use since shortly after its initial synthesis in the 1920’s, but was formally approved for use in combination with acetaminophen in the United States in 1998.  Current indications are for treatment of moderate-to-moderately severe pain (combinations with acetaminophen or ibuprofen) or alleviation of cough and symptoms of upper respiratory tract infections (combined with chlorpheniramine or homatropine).  It is currently one of the most commonly prescribed drugs in medical practice.  Hydrocodone is available in multiple formulations (tablets, capsules, syrup) combined with other analgesics, antihistamines or anticholinergics in concentrations of 2.5, 5, 7.5 and 10 mg generically and (with acetaminophen) under brand names such as Vicodin, Norco, Lortab and Co-Gesic, among others.  The preparations are generally taken every 4 to 6 hours.  Importantly, the dose of acetaminophen in hydrocodone combinations varies from 300 to 1000 mg per tablet.  The FDA, however, has recommended that physicians not use opioid combinations with concentrations of acetaminophen of more than 325 mg per unit dose.  Side effects of hydrocodone include sedation, respiratory depression, mental clouding, euphoria, agitation, constipation, diarrhea, abdominal bloating, nausea, vomiting, headache and dizziness.  Long term use can be followed by withdrawal symptoms.  Hydrocodone is a controlled substances and classified as a Schedule III drug, indicating that it has medical usefulness, but also a potential for physical and psychological dependency and abuse.


Hepatotoxicity

Despite wide scale use for many decades, hydrocodone by itself has not been convincingly linked to instances of clinically apparent acute liver injury.  However, when combined with acetaminophen, hydrocodone combinations have become a common cause of acetaminophen acute liver injury.  The typical history is of a patient who began taking more than the prescribed number of pills over several days, attempting to achieve more of an opiate effect and leading secondarily and unintentionally to an overdose of acetaminophen.  Because of the potential for hepatotoxicity, the FDA has warned against the use of opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet.
(Seehttp://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm.)

Hydrocodone, like other opiates, is metabolized in the liver by the P450 microsomal oxidizing enzyme system, and levels can be significantly affected by either inhibitors of CYP 3A4 (which increase levels and can lead to toxicity) or inducers of the enzyme (which decrease levels and can affect efficacy).

References on the safety and potential hepatotoxicity of hydrocodone are given in the Overview section of the Opioids.


Drug Class:  Opioids


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