[india-drug] Re: B6 and INH (3)

["Sampada Patvardhan" <dicmspc@yahoo.co.in>]

B6 and INH (3)
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  Dear Dr.Pranav
   
  Here is information in response to your query about: What dose of Pyridoxine (B6) should be prescribed with INH to prevent peripheral neuritis?
   
  Chronic ingestion of therapeutic doses is associated with many untoward effects including peripheral neuropathy, hepatitis, optic neuritis, and encephalopathy. The normal therapeutic dose of INH is 5 mg/kg/day to a maximum of 300 mg/day. Up to 10 mg/kg/day (600 mg/day) are occasionally used in severely ill patients. The incidence of adverse effects is about 5.4%. Peripheral neuropathy occurs most often in patients who are slow acetylators, and those who are malnourished, alcoholic, uremic or diabetic. It is also dose related, occurring in 44% of patients receiving more than 16 milligrams/kilogram/day.
   
   
  a) If acute INH overdose (acute ingestion of greater than 80 milligrams/kilogram) is suspected, even in an asymptomatic patient, the administration of intravenous pyridoxine should be strongly considered. 
  b) The earlier pyridoxine is administered in an isoniazid overdose the fewer the complications 
  c) It is recommended that all Emergency departments have adequate stocks of pyridoxine (5-10 grams) on hand at all times. 
   
  DOSE 
  a) In severely symptomatic patients with seizures, acidosis, an), pyridoxine should be given intravenous push until seizures are controlled and coma resolves. 
  b) DOSE - Administer an amount of pyridoxine equivalent to the estimated amount of INH ingested. Initially administer up to 5 grams over 30 to 60 minutes. If necessary, the remainder may be given by intravenous drip in 500 to 1000 milliliters D5W over the next one to two hours 
  c) If the amount of INH ingested is unknown, administer 5 grams of intravenous pyridoxine and repeat as needed until seizures are controlled. 
  d) The maximum nontoxic pyridoxine dose is unknown. 
   
  ADVERSE EFFECTS 
  a) Pyridoxine can be neurotoxic in large doses. Administration of 0.2 to 5 grams for 2 to 40 months has produced neuropathy. In isoniazid overdose, single intravenous doses of 70 to 357 milligrams/kilogram given over 1 hour and up to 52 grams have been administered without development of toxicity. 
  b) Current references only recommend administration of the amount of pyridoxine equivalent to the amount of isoniazid ingested, with no maximum dose stated. 
  c) In a randomized, controlled crossover trial with 5 healthy volunteers, the effects of intravenous pyridoxine (5 g) on acid-base status were assessed. A statistically significant increase in base deficit compared to placebo was noted at 3, 10, and 20 minutes, with mean maximal increase in base deficit observed at 3 minutes (2.74 mEq/L). It is suggested that larger pyridoxine infusions, such as those given in overdose, may have the potential to cause some degree of metabolic acidosis. 
  d) One study reports the use of 10 grams of pyridoxine in a 24-year-old who ingested a "mouthful" of hydrazine. One week later the patient developed paresthesias of his hands and feet and mild distal limb weakness. Three weeks post injection he had diminished pinprick, vibration, touch and position senses in his distal arms to the wrists and distal legs to the ankles. The neuropathy spontaneously cleared over the next 6 months. Although the neuropathy may have been due to the hydrazine, the symptoms are similar to those of pyridoxine toxicity. 
   
  PRESERVATIVES - Excipient toxicity and adverse effects from intravenous pyridoxine hydrochloride products (standard dose of 5 to 10 grams) are expected to be minimal. 
  f) A 5- to 10-gram dose of pyridoxine hydrochloride contains 250-500 mg of chlorobutanol (therapeutic dose 300-1200 mg/day). Chlorobutanol may cause mild CNS depression. 
  g) A 5- to 10-gram dose of pyridoxine hydrochloride contains 1 to 2 mg of parabens per kilogram. Since this amount is well below the World Health Organization's estimated total acceptable daily intake of 10 mg/kg for methylparaben, ethylparaben, and propylparaben, no acute toxicity is expected. Paraben-induced hypersensitivity reactions have been reported. 
   
  Source: Thomson Micromedex, USA
   
  Sent by:
  Dr. (Mrs.) Sampada Patvardhan (Ph.D.Tech. Pharmacology)                                         
  Director, Maharashtra State Pharmacy Council?s Drug Information Centre  E.S.I.S. Hospital Compound, L.B.S. Marg, Mulund (W), Mumbai-400 080   Phone: 25930607  Telefax: 25684291/25684418  e-mail: dicmspc@yahoo.co.in  OR dicmspc@hathway.com