Pabrinex (parentrovite) duration of usage based on indicatons

Treatment of acute Wernicke-Korsakoff syndrome

• Two pairs of Pabrinex 5mL ampoules should be administered three times daily for two days. 
• If there is no clinical response after two days (six doses), treatment should be discontinued. 
• If clinical improvement is seen the contents of one pair of 5mL Pabrinex ampoules should then be administered three times daily for a further three days or for as long as clinical improvement continues.

High risk of Wernicke-Korsakoff syndrome. 

• One pair of Pabrinex 5mL ampoules administered three times daily for two days. 
• Following the initial intravenous loading dose, oral supplementation should begin with thiamine 100mg three times daily.
• This should be reviewed prior to discharge.

Rapid therapy of severe depletion or malabsorption of water soluble vitamins B and C, particularly in alcoholism

• 2 to 3 pairs of 5ml ampoules (1 pair = ampoule 1 + ampoule 2) diluted with 50ml to 100ml of infusion solution and injected over 30 minutes at intervals decided by your doctor (typically every 8 hours).

Psychosis following unconsciousness from a narcotic drug (narcosis) or electroconvulsive therapy, or poisoning from infection

• 10ml of the mixed vials (1 pair) injected twice daily for up to 7 days.

Haemodialysis patients

• 10ml of the mixed vials (1 pair) injected at the end of dialysis, once every 2 weeks.  

 Refeeding syndrome

• Pabrinex one to two pairs once to three times daily for 3 to 5 days (use the higher more frequent dose for chronic alcohol abusers.

REFERENCE

NHS Grampian

(http://www.nhsgrampian.com/grampianfoi/files/VitSupAC_503_1111.pdf)

Intensive Care Society Of Ireland 

(http://www.criticalcarenutrition.com/docs/BOB/ENPNGuideline.pdf)

Beaumont Hospital's Intensive Care Unit's

(http://www.criticalcarenutrition.com/docs/BOB/BeaumontGuidelines.pdf

Product Leaflet

BNF

Rationale for Oral Vitamin K (Paeds)

Background

• Vitamin K is necessary for synthesis of factors II (prothrombin), VII, IX, and X
• Vitamin K is undetectable in cord blood
• Lactobacillus (primary gut flora in breastfed babies) does not synthesize vitamin K
• Breastmilk contains only small amounts of vitamin K (1 – 9 mcg/L); formula (53-66 mcg/L)

Oral Regimens

• there is no licensed PO form in US, but parental form can be given orally
• in countries that have gone to PO prophylaxis, failures (even with good compliance) have been reported .  Failures have not been reported with IM prophylaxis.
• since multiple doses are required, compliance is an issue
• advise parents regarding the increased risk of VKDB (exact numbers are unknown)
• maternal dietary changes have little effect on overall vitamin K status of newborn
• maternal vitamin K supplements of 5mg/day (800% RDA) has been shown in one study to raise infant serum levels to near formula-fed levels, but there is no FDA approved MVI that contains this amount of vitamin K

Absorption and Dose:

• No specific recommendation on long term prophylactic dose of Vitamin K
• oral administration vitamin K1 is absorbed from the small intestine.
• The systemic availability following oral dosing is approximately 50%, with a wide range of interindividual variability. Absorption is limited in the absence of bile.
• 2.5 to 5 mg orally once every 24 hours
• Product leaflet recommends similar dose as per IM as the onset of action of action is approximately same for both the route
• In terms of absorption, response to oral phytonadione is only slightly slower than response to the intravenous form
• neonatal liver disease/ billiary atresia : 1mg OD

References:

1. BNF for Children 2013
2. http://www.medicines.ie/medicine/3250/SPC/Konakion+MM+Paed+Amps/
3. http://www.drugs.com/dosage/phytonadione.html
4. http://newborns.stanford.edu/VitaminK.html
5. http://www.medsafe.govt.nz/profs/puarticles/vitk.htm

Absorption of Folate

• Folate is a water-soluble B vitamin
• Absorption at proximal part of small intestine
• About 85% of supplemental folic acid, when taken with food, is bioavailable
• When consumed without food, nearly 100% of supplemental folic acid is bioavailable

People with alcohol dependence

• People with alcohol dependence frequently have poor-quality diets that contain insufficient amounts of folate. 
• Moreover, alcohol interferes with folate absorption and metabolism and accelerates its breakdown 
• Even moderate alcohol consumption of 240 ml (8 fluid ounces) red wine per day or 80 ml (2.7 fluid ounces) vodka per day for 2 weeks can significantly decrease serum folate concentrations in healthy men

People with malabsorptive disorders

• tropical sprue, celiac disease, and inflammatory bowel disease—might have lower folate absorption than people without these disorders 
•  Diminished gastric acid secretion associated with atrophic gastritis, gastric surgery, and other conditions can also reduce folate absorption

Reference

1. Lexicomp
2. http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

Absorption of vitamin B12

• Vitamin B12, also known as cyanocobalamin, is a water-soluble vitamin
• Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed
• absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12)
• Existing evidence does not suggest any differences among forms with respect to absorption or bioavailability. 
• However the body’s ability to absorb vitamin B12 from dietary supplements is largely limited by the capacity of intrinsic factor- only about 10 mcg of a 500 mcg oral supplement is actually absorbed in healthy people

Individuals who have had gastrointestinal surgery

• removal of all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid and intrinsic factor 
• This reduces the amount of vitamin B12, particularly food-bound vitamin B12 that the body releases and absorbs. 
• Surgical removal of the distal ileum also can result in the inability to absorb vitamin B12. 

Additional Information (combination with Folate)

• Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency
• Preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency
• Permanent nerve damage can occur if vitamin B12 deficiency is not treated. 
• For these reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy adults

Reference:
http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

Can folic acid be substituted with folinic acid?

• Folic Acid and folinic acid are forms of vitamin B9. 
• The human body needs folate to perform many functions, including cell division, growth, and the production of new red blood cells. 
• Folinic acid is chemically different to folic acid but both work in a similar way
• Folinic acid is a metabolically active reduced form of folate that bypasses dihydrofolate reductase
• It has an important role in the treatment of methotrexate overdose and acute bone marrow toxicity, due to its faster action and independence of dihydrofolate reductase

Substitution in Toxoplasmosis:

• Toxoplasma cannot take in folinic acid, but can absorb folic acid, thereby partially bypassing the synergistic activity of pyrimethamine and sulphonamide.
• Hence folinic acid should be used to prevent toxicity and folic acid should be avoided since it might thwart the therapeutic effect.

References:

1. Toxoplasmosis A Comprehensive Clinical Guide by D.H.M Joynson and T.G Wreghitt 2005 pg 322

What is the preferred treatment which covers PCP & Toxoplasmosis?

Bactrim (TMP 15-20 mg and SMX 75-100 mg/kg/day) given 6 or 8 hourly for 6 weeks

• This is the first line treatment for PCP 
• Toxoplasmosis second line treatment regime is Bactrim (TMP 5 mg/kg and SMX 25mg/kg) IV or PO BD

OR

• Sulfadoxine/Pyrimethamine 500/25mg (Fansidar) PO 1 tab q12h + Folinic Acid 10-25mg PO q24h + Clindamycin 600mg IV/PO q6h for at least 6 weeks
• This is first line treatment for Toxoplasmosis 
• Second line treatment for PCP involves Pyrimethamine (Leucovorin) + Clindamycin 600mg IV/PO q6h
• Pyrimethamine dose : 200mg PO once then followed by body weight: ≤ 60kg 50mg PO daily, > 60kg 75mg PO daily

References: 

1. Aidsinfo.nih.gov/guidelines
2. National Antibiotic Guideline 2014

Interaction Between Bactrim and Folinic Acid

HIV patient currently being treated for PCP and Toxoplasmosis

• First line treatment for PCP involves bactrim which has a major interaction with the first line treatment of toxoplasmosis which uses folinic acid
• Interaction between folinic acid and bactrim
• Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for the treatment of HIV positive patients with Pneumocystis jiroveci pneumonia in a randomized placebo controlled trial. 
• Co-administration of trimethoprim-  sulfamethoxazole and leucovorin during treatment of Pneumocystis jiroveci pneumonia should be avoided. 

References:

1. http://www.drugs.com/disease-interactions/sulfamethoxazole-trimethoprim,bactrim.html
2. http://www.rxlist.com/bactrim-drug/warnings-precautions.htm
3. LEXICOMP