Conversions : Amoxicillin to Phenoxymethyl Penicillin

• In contrast to narrow spectrum penicillin G and V, amoxicillin has got a wide antibiotic spectrum and is effective against some gram negative rods too
• Penicillin G and penicillin V are quite similar to each other but penicillin V is less effective against gram negative bacteria as compared to penicillin G

Disease specific

• Amoxicillin is at least as effective as penicillin V for the treatment of streptococcal pharyngitis in children
• Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia in children aged 3-59 months
• Both penicillin and amoxicillin are considered the first line of treatments for odontogenic infections.

Dosing for Pen V

• The dosage and frequency of Phenoxymethylpenicillin depends on the severity and localisation of the infection and expected pathogens.
• Phenoxymethylpenicillin Solution should be taken at least 30 minutes before or 2 hours after food, as ingestion of Phenoxymethylpenicillin with meals slightly reduces the absorption of the drug.
• Phenoxymethylpenicillin 250mg is approximately equivalent to 400,000 units.
• Adults/children over 12 years: 250mg - 500mg every six hours
• Children: Infants (up to 1 year): 62.5mg every 6 hours
• 1-5 years: 125mg every six hours
• 6-12 years: 250mg every six hour

References

1. http://www.emedexpert.com/compare-meds/amoxicillin-vs-penicillin.shtml
2. http://medlicker.com/869-penicillin-vs-amoxicillin
3. http://www.straighthealthcare.com/antibiotic-chart.html#penicillins
4. https://www.medicines.org.uk/emc/medicine/27478

Aspirin : Rheumatic Fever in Obese Patient

• No sufficient information on the pharmacodynamics in obese patients
• Based on a single dose study, distribution of salicylate into that fraction of body weight which is in excess of ideal weight-presumed to consist mainly of adipose tissue is proportionately less than its distribution into ideal weight.
• This is consistent with the physicochemical profile of salicylate that demonstrates its relatively nonlipophilic character
• Apparent clearance of salicylate, likewise, was minimally influenced by obesity
• However, peak salicylate concentrations averaged 26% lower in the obese volunteers due to their larger v d . Since the efficacy of aspirin following single doses for the acute treatment of pain or inflammation probably is related to the peak serum concentration, the findings suggest that obese individuals require higher doses in these circumstances

Dosing Recommendations

• No specifc guides for obese/overweight patients
• typical doses of aspirin used to reduce fever and alleviate arthritis symptoms are
• 80 to 100 mg/kg per day in divided doses every four hours in [children]
• 4 to 8 g/day in adults in divided doses every four to six hours.
• However, many experts recommend starting at a lower dose of 50 to 60 mg/kg/day in children because of the risks of salicylate toxicity characterized by tinnitus, headache, and tachypnea

References:

• INFLUENCE OF AGE, GENDER, AND OBESITY ON SALICYLATE KINETICS FOLLOWING SINGLE DOSES OF ASPIRIN. Arthritis and Rheumatism, Vol. 29, NO. 8 (August 1986)
• www.uptodate.com

Conversion : Quetiapine SR to IR

• There is little published evidence to guide clinicians on the best method of switching between quetiapine XL and quetiapine IR tablets. 
• Any switch should be fully discussed with the individual and carer, combined with increased monitoring for adverse events.
• In general a straight swap from once daily to twice daily IR is appropriate1 but may be associated with a slightly higher risk of sedation and postural hypotension following the switch. 
• If sedation and postural hypotension are a concern clinicians may wish to consider giving a larger dose in the evening (see table 1). 
• Although other pharmacokinetic parameters are similar the peak plasma concentration for quetiapine XL = 5-6 hours, while IR = 1 hour.

References:

• Switching from quetiapine XL to quetiapine immediate release. Advice for health professionals. Southern Health, NHS Foundation Trust.

Strength of Bulk Preparation in HKGU

 

Hypercholesterolemia : Pregnancy & Breastfeeding

Drugs	Pregnancy	Breastfeeding
Atorvastatin Simvastatin Rosuvastatin	·         Category X ·         Animal studies have failed to reveal evidence of teratogenicity ·         Use in women who are or may become pregnant is contraindicated ·         Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol products are essential for fetal development.	·         Use is contraindicated ·         has been detected in human milk. ·         potential for serious adverse events in nursing infants and the concern over disruption of infant lipid metabolism
Ezetemibe	·         Category C ·         Animal studies have revealed evidence of increased incidences of abnormal skeletal findings at higher doses. ·         There are no controlled data in human pregnancy	·         Use should be avoided ·         Due to concern over disruption of infant lipid metabolism, other agents are preferred, especially while nursing a newborn or preterm infant.
Fenofibrate	·         Category C
Cholestyramine	·         Category C ·         not absorbed after oral administration, direct fetal harm is not expected. Impairment of absorption of fat soluble vitamins and other nutrients as well as effects of reduced lipid concentrations may be of concern ·         drug has been used successfully during pregnancy. ·         only be given during pregnancy when benefit outweighs risk	·         not absorbed after oral administration and therefore is not expected to be present in human milk ·         While adverse effects in the breast-feeding infant are unlikely, altered absorption of fat soluble vitamins and other nutrients by the mother may effect the integrity of the milk.
Colestipol	·         not  formally assigned by the FDA ·         Because colestipol is not absorbed after oral administration, direct fetal harm is not expected. ·         Impairment of absorption of fat soluble vitamins and other nutrients as well as effects of reduced lipid concentrations may be of concern
Colesevelam (bile acid sequestrant)	·         Category B ·         used only if clearly needed ·         Requirements for vitamins and other nutrients are increased during pregnancy, however, the effect of this drug on the absorption of fat-soluble vitamins has not been studied in pregnant women	·         Use is considered acceptable ·         nonabsorbable resin ·         does not enter the nursing mother's bloodstream, it will not reach the infant via breast milk.

Recommendation

• Since atherosclerosis is a chronic process, discontinuation of lipid-lowering drugs during pregnancy should have little impact on long term outcomes of primary hypercholesterolemia therapy.
• FH women who are on statin therapy and anticipate becoming pregnant should stop statins three months prior to attempting to conceive
• For breastfeeding, use of lipid lowering drugs is for long-term maternal benefits and temporary interruption of therapy is not usually considered to significantly impact on maternal morbidity or mortality
• bile acid sequestrants, cholestyramine and colestipol are expected to be safe in breastfeeding because they are not absorbed from the maternal gastrointestinal tract. These would be the preferred options for breastfeeding mothers
• However, the possibility of maternal (and infant) deficiencies in fat-soluble vitamins should be considered.

References:

• www.drugs.com
• www.uptodate.com
• Safety of Statins in Breastfeeding. 2002. Drug Information Service at Christchurch Hospital

Acinetobacter : Oral vs Parenteral Unasyn

• T. Unasyn 375mg(sultamicillin- ampicillin 220mg, Sulbactam 147mg)
• Inj Unasyn 1.5g (ampicillin 1g, Sulbactam 0.5g )

Sensitivity

• β-Lactamase inhibitors, including sulbactam, bind to β-lactamase, thereby increasing the susceptibility of the microorganism to co-administered β-lactam antibiotics.
• most β-lactamase inhibitors do not exert antimicrobial activity if given alone
• Sulbactam, however, has been demonstrated to have antimicrobial properties, including against A. baumannii, which are thought to be mediated by binding to penicillin binding-proteins
• Although the available evidence suggests that sulbactam-based therapies can be effective for the treatment of A. baumannii infection, there is little evidence to suggest that sulbactam-based therapies are more or less effective than alternative therapies

Dose

• Ranges from 3g QID to 3g 3 hourly (suspected MDR pathogens)

Coversions to Oral dose

• No supporting evidence or guidelines on use of oral Unasyn for eradication therapy
• No guides on dose equivalence/conversion of IV to oral for management of Acinetobacter
• As A baumannii is intrinsically multidrug resistant, it is highly recommended to achieve sufficient levels by using therapeutic doses of IV Unasyn ( compared to Oral/ which may not achieve the required sulbacam doses based on usual IV to Oral conversions)

References:

1.   http://www.sciencedirect.com/science/article/pii/S1413867013000718

2.   http://www.globalrph.com/Acinetobacter-baumannii.htm

3.   Guide to Antimicrobial Therapy in Adults 2012

4.   www.uptodate.com

5.   http://emedicine.medscape.com/article/236891-medication

Enoxaparin: OD vs BD dosing regimen in Cancer Patients

• Two enoxaparin dosing schemes are FDA-approved for the treatment of DVT with or without PE in hospitalizedpatients:
• enoxaparin 1 mg/kg SC every 12 hours
• enoxaparin 1.5 mg/kg SC every 24 hours

Rationale in Cancer Patient

• Currently, no study has directly compared enoxaparin 1.5 mg/kg SC once daily versus 1 mg/kg SC twice daily as the primary outcome for the long-term treatment of VTE in cancer patients
• Based on the results of the Merli trial, the ONCENOX trial, and the CANTHANOX trial which showed higher rates of major bleeding from using 1.5 mg/kg SC once daily versus 1 mg/kg SC twice daily, we recommend that in patients at a higher risk of bleeding that 1 mg/kg SC twice daily dosing of enoxaparin be used. 
• (patients at a higher risk of bleeding, thrombocytopenia, brain metastases, young female during menstruation with or without thrombocytopenia)
• We hypothesize that the seemingly higher bleeding rate may be due to achieving higher peak plasma anti-Xa concentrations.
• One meta-analysis evaluated 1522 cancer and non-cancer patients from five studies who received either once- or twice-daily LMWH and concluded that once daily dosing appears to be as safe and effective as twice daily dosing; however, the possibility of a higher frequency of fatal bleeding with once daily therapy could not be excluded
• several patient-specific factors that may be used to help balance efficacy, bleeding risk, cost, and convenience for cancer patients being treated with enoxaparin for VTE
• Factors which indicate higher-risk for both recurrent VTE and bleeding among cancer patients and which may suggest an advantage for twice daily enoxaparin therapy include prior VTE, certain concomitant medications (hormonal or chemotherapy), chemotherapy-induced thrombocytopenia, poor performance status, obesity, large ileofemoral DVT, and massive PE
• In addition, patients with brain tumors or metastases have a particularly higher risk of hemorrhage with anticoagulation therapy, which carries up to a 45% incidence of mortality in the event of a bleed.
• Therefore, we recommend enoxaparin 1 mg/kg SC twice daily dosing for these high-risk patients in order to minimize risk of intracranial hemorrhage
• In contrast, patients without these high-risk factors or patients with renal dysfunction in whom higher
• total-dose LMWH (twice daily enoxaparin) may increase bleeding risk may benefit from once-daily dosing
• patients with severe renal dysfunction (creatinine clearance <30 mL/min) require lower doses such as enoxaparin 1 mg/kg SC once daily.

Recommendation