Interacting drugs - summary

+ Metronidazole-

 Barbiturates

 barbiturates decrease the antimicrobial effectiveness of metronidazole

Cimetidine

 decreased metronidazole clearance and increased serum level occur

Metronidazole +

Anticoagulants

 increase the anticoagulant effect of Warfarin oranisindione Risk of bleeding increased

Disulfram

  concurrent use may result in acute psychosis or confusional state

Ethanol

 Disulfram-like reaction including symptoms of flushing, palpitations, tachycardia, nausea,vomiting, etc may occur with concurrent use. Caution is advised.

Hydantoins

 total clearance of Hydantoin decreased and its elimination half-life prolonged

Lithium

 in patients stabilised on relatively high Lithium doses, short term metronidazole has been associated with increased lithium levels and toxicicity in some cases

Drug /Lab interactions-
the drug may interfere with chemical analyses for AST, ALT, LDH, triglycerides and hexokinase  glucose. Zero vlaues may occur.ses

Renal/GU-

Dysuria,cystisis, polyuria, incontinence, sense of pelvic pressure, proliferation of Canida in  the vagina, dysparenuia, decreased libido. Darkened urine deep red-brown-colour has been reported.
 The pigment appears to be a metabolite of metronidazole and it seems to have no significance.

Local-

Thrombophelebitis,after IV infusion can be minimised or eliminated by prolonged use of in dwelling IV catheters.

CNS-

Seizures, peripheral neuropathiy.the latter characterrised mainly by numbness or paresthesia of  an extrtemity, dizziness, vertigo,incoordination, ataxia, confusion, irritabiliry, depression,weakness, insomnia, headache, syncope.

GI-

Nausea sometimes accompanied by headache, anorexia, and occassionally vomiting., diarrhea, epigastric distress, abdominal cramping, constipation, proctitis, sharp unpleaseant metallic taste, a modification of the taste of alcoholic beverages, furry tongue, glossitis, stomatitis (these may be  associated with a sudden overgrowth of canidida)

Hematologic-

Reversible neutropenia, (leukopenia)  reversible thrombocytopenia (rare)  
            
Cardiovascular

 Flattening of the T-wave may be seen in ECG tracings

Hypersensitivity-

Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth
(or vagia or vulva) fever

Miscellaneous-

Fleeting joint pains, sometimes resembling "serum sickness " . One case of
metronidazole induced pancreatitis reported

Blood dyscrasias.Active CNs disease,hypersens,serious neurological disease and seizures.

Special precautions:

Pregnancy. Lactation. Avoid alcohol, renal/hepatic impairment

Crohns disease- patients are known to have an increased incidence of GI and certain extraintestinal  cancers. There have been some reports in the medical literature of breast and colon cancer in Crohns disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and relation effect has not been established.

Candidiasis- known or previously unrecongnized, may present more prominent symptoms during  therapy and requires treatment with candicidal effect.

Hematologic effects- metronidazole is a nitronidazole , use with care in patients with a history of blood  dyscrasia. Mild leukopenia has been seen during administration, however no persistent hematologic  abnormalities attributabled to the drug has been reported. Perform total and differential count before  and after therapy.

Amebic liver abscess- metronidazole does not obivate the need for aspiratin of pus

Drug /Lab interactions-
the drug may interfere with chemical analyses for AST, ALT, LDH, triglycerides and hexokinase  glucose. Zero vlaues may occur.

Warnings-

Neurologic effects- seizures (associated with high cumulative doses ) and periphral neuropathy  (characterised by numbness or paresthesia of an extremity ) have occured. Carefully monitor patients  receiving high doses for long periods eg Crohns disease patients

Hepatic function impairment- patients with hepatic disease metabolize metronidazole slowly.  Accumulation of the drug or its metabolites may occur. Cautiously administer doses below those  usually recommended.

Carcinogenesis- metronidazole has shown evidence of carcinogenic activity with chronic oral  administration in rodents

Elderly- since the pharmacokinetics of metronidazole may be altered in the elderly, monitoring of serum levels may be necessary to adjust dosage accordingly.

Pregnancy- restrict metronidazole for trichomoniasais in the second and third trimesters to those in whom local palliative treatment has been inadequate.

Lactation- safety for use in nursing mother has not been established

Children- safety and efficacy in children has not been established

Indications:
Amebiasis

Dosage:

Acute cases - 750mg  3 times daily for  5 to  10 days, others- 500 to 750mg  3 times daily.
Children- acute cases- 35 to 50mg/kg/24 hours (maximum 750mg dose) in  3 divided  doses for  10 days
7 day course treatment -
Adults- 250mg 3 times daily for 7 consecutive days.
Children- 5mg/kg/dose 3 times daily for 7 days.

Overdosage- Symptoms                                              

Nausea, vomiting, and ataxia.                                            
Single oral doses upto 15g have reported in suicide             
attempts accidental overdosage

   Treatment

1. No specific antidote  exists.
 2. Treatment consists of usual supportive measures.

Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing   schedule.
3. Do not double doses. 

METRONIDAZOLE

1.May cause GI upset, take with food. Avoid alcoholic beverages.
2. Complete full course of therapy,take until gone. may cause darkening of urine.
3.An unpleasant metallic taste may be noticeble

4.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to metronidazole.   Also tell your doctor if you are allergic to any other substances, such as foods, presrvatives or dyes.
  
5.Pregnancy - metronidazole given by mouth has not been shown to cause birth defects or problems in  animal studies. 
 
6.Breast feeding-  the small amounts of this medicine that are absorbed are unlikely to cause serious    problems  in nursing babies. 

7. Children - rosacea is usually considered an adult disease. Therefore, topical metronidazole is not  generally  used in children.
 
8. Elderly-  there is no specific information comparing use of topical metronidazole in the elderly with  use in  other age groups. 
   
9. Other medicines -    Tell your doctor if you are taking any other  medicines. Your doctor may want to change  the dose  or other precautions may be necessary.

     Anticoagulants - patients taking medicines anticoagulants with metronidazole may have an   increased chance of bleeding.

 10. Other medical problems -

   Tell your doctor if you have any other medical problems especially -

    Blood disease or history of blood disease- metronidazole may make the condition worse
    Central nervous system - metronidazole may increase the chance of seizures or other CNS side      effects.

       
11. Missed dose -    If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time   for the next dose, skip the missed dose. Do not double doses.

12. Storage -   Keep out of reach of children. Store away from heat or direct sunlight. Do not store  the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines -  Do not keep outdated medicine or medicine no longer needed. Be sure that any  discarded medicine is out of reach of children.

Pharmacology:

Metronidazole, a nitroimidazole derivative is active against anaerobic bacteria and protozoa. Its mode of action is not understood. It appears to enter the cells of micro-organisms that contains nitroreductase,where a nitro group is reduced. Unstable intermediate compounds are formed which binds DNA and inhibiting synthesis,causing cell death.

Pharmacokinetics:

Well absorbed after oral administration. Peak serum levels occurs at about 1 to 2 hours. Oral bioavailability is not affected by food. Elimination of metronidazole is via urine(60 to 80% of the dose); fecal excretion accouts for 6 to 15%.

Not significant

Pregnancy:

There are noadequate and well controlled studies in pregnant woman. Use during pregnancy only if clearly needed.

Lactation:

Safety for use in nursing mother has been established. Children; Safety and efficacy in children have not been established except for the treatment of amoebiasis.