Albendazole in Breastfeeding & Pregnancy

Albendazole in Breastfeeding

Yes

Use with Caution

Use of Albendazole in Children

Albendazole in Pregnancy

.

All information was accessed on 30 August 2019 by JCK Ho

Prednisolone in Neurosyphillis

UK national guidelines on the management of syphilis 2015	Steroids should be given with all anti-treponemal antibiotics for cardiovascular syphilis; 40–60 mg prednisolone OD for three days starting 24 h before the antibiotics.
Syphilis: diagnosis and management options [The Pharmaceutical Journal, 20 Mac 2018]	Steroids should be given with all treatment regimens for late syphilis with cardiovascular or neurological involvement; 40–60mg prednisolone OD for three days starting 24 hours before antibiotics
https://www.bashhguidelines.org/current-guidelines/genital-ulceration/syphilis-2015/	Steroids should be given with all anti-treponemal antibiotics for neurosyphilis; 40–60mg prednisolone OD for three days starting 24h before the antibiotics.
2014 European Guideline on the Management of Syphilis	• Prednisolone can prevent the febrile episode Although steroids are unproven at ameliorating local infection, biological plausibility suggests that those may help preventing severe deterioration in early syphilis with optic neuritis and uveitis. • Management: - If cardiovascular or neurological involvement (including optic neuritis) exists, inpatient management is advisable. - Prevention of Jarisch-Herxheimer reaction: Prednisolone 20-60 mg daily for 3 days, starting anti-treponemal treatment after 24 hours of commencing prednisolone [IV; C] - Antipyretics
https://www.medscape.com/answers/1169231-113753/how-is-a-jarisch-herxheimer-reaction-to-neurosyphilis-therapy-managed [Updated 17 July 2018]	Corticosteroids (eg, prednisone at 20 mg 4 times per day for 3 d started 1 d prior to antitreponemal treatment) have been used to prevent adverse effects. Salicylates/antipyretics are prescribed for symptomatic relief.
National Antibiotic Guideline (Malaysia) 2014	All patients with neurosyphilis should be considered for corticosteroid cover at the start of the therapy to prevent the Jarisch-Herxheimer reaction (Prednisolone 10-20mg PO q8h for 3 days commencing one day prior to syphilis treatment)

All accessed on 22 Aug 2019 by JCK Ho

New Primaquine Dosing Recommendation for Non-complicated P. falciparum Malaria

UptoDate: Treatment of uncomplicated falciparum malaria in nonpregnant adults and children

[Updated at 31 July 2019]

Gametocytes may persist in the blood after successful treatment of infection; they are not harmful to the patient but serve as a source of ongoing transmission. Artemether-lumefantrine has been shown to be superior to non-artemisinin antimalarial drugs in reducing gametocytemia. Primaquine has activity against mature gametocytes but no effect on blood-stage parasites.

To further reduce transmissibility of treated P. falciparum infection in endemic areas with low transmission, we are in agreement with the WHO which favors administration of primaquine (0.25 mg/kg single dose) on the first day of malaria treatment to nonpregnant adults and children ≥6 months. This approach is supported by a systematic review including 24 randomized trials in which a single low dose of primaquine added to ACT therapy reduced infectiousness of humans to mosquitoes on day 3 or 4 (from 14 to 2 percent) and was as effective as higher doses of primaquine. Data on the impact on community transmission levels and hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency are needed. Primaquine should be avoided in pregnant women and infants <6 months of age given the particular vulnerability of these patient groups.

Primaquine can cause hemolysis in individuals with G6PD deficiency; however, G6PD testing is not required for patients receiving primaquine for reducing transmissibility given the relatively low dose for this indication. In one study including 274 Senegalese patients with mild malaria randomized to ACT plus primaquine (0.25 mg/kg, single dose) versus ACT alone, the mean reduction in hemoglobin at day 7 was equivalent. Among 54 patients with G6PD deficiency, the drop in hemoglobin was 0.63 g/dL greater in those who received primaquine than in those who received an ACT alone.

World Health Organisation: Guidelines for the Treatment of Malaria (3^rd Edition, 2015)

In low-transmission areas, give a single dose of 0.25 mg/kg bw primaquine with ACT to patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) to reduce transmission. Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is NOT required. 

(Strong recommendation, low quality evidence)

Human Albumin Injection in Hepatorenal Syndrome (HRS)

UptoDate: Hepatorenal syndrome

The ideal therapy for hepatorenal syndrome is improvement of liver function from recovery of alcoholic hepatitis, treatment of decompensated hepatitis B with effective antiviral therapy, recovery from acute hepatic failure, or liver transplantation. The ability of liver function to improve with abstinence from alcohol and effective antiviral therapy of hepatitis B is remarkable.

However, when improvement of liver function is not possible in the short term, we recommend that medical therapy be instituted in an attempt to reverse the acute kidney injury associated with hepatorenal syndrome.

In patients with hepatorenal syndrome who are critically ill, we suggest initial treatment with norepinephrine in combination with albumin. Norepinephrine is given intravenously as a continuous infusion (0.5 to 3 mg/hr) with the goal of raising the mean arterial pressure by 10 mmHg, and albumin is given for at least two days as an intravenous bolus (1 g/kg per day [100 g maximum]). Intravenous vasopressin may also be effective, starting at 0.01 units/min and titrating upward as needed to raise the mean arterial pressure.

In patients with hepatorenal syndrome who are not critically ill, where terlipressin therapy is not available, we suggest initial treatment with a combination of midodrine, octreotide, and albumin. Midodrine is given orally (starting at 7.5 mg and increasing the dose at eight-hour intervals up to a maximum of 15 mg by mouth three times daily), octreotide is either given as a continuous intravenous infusion (50 mcg/hr) or subcutaneously (100 to 200 mcg three times daily), and albumin is given for two days as an intravenous bolus (1 g/kg per day [100 g maximum]), followed by 25 to 50 grams per day until midodrine and octreotide therapy is discontinued.

In patients who fail to respond to the above therapies, develop severely impaired renal function, and either are candidates for liver transplantation or have a reversible form of liver injury and are expected to survive, we recommend dialysis as a bridge to liver transplantation or liver recovery.

In patients treated with norepinephrine, terlipressin, or octreotide, we usually treat for a total of two weeks. However, we and others occasionally treat for longer durations (up to one month or more) if there is some but not complete improvement in renal function after two weeks of therapy. In patients who respond to therapy, we occasionally treat indefinitely with midodrine to maintain a higher mean arterial pressure (or until liver transplantation or resolution of liver injury). Many patients who recover from type 1 hepatorenal syndrome continue to have refractory ascites, and midodrine may be effective in such patients [42]. In contrast, if a patient has no improvement in renal function after two weeks, therapy with these drugs can be considered futile.

EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis

Management of hepatorenal syndrome

The most effective method currently available is the administration of vasoconstrictor drugs. Among the vasoconstrictors used, those that have been investigated more extensively are the vasopressin analogues particularly terlipressin. The rationale for the use of vasopressin analogues in HRS is to improve the markedly impaired circulatory function by causing a vasoconstriction of the extremely dilated splanchnic vascular bed and increasing arterial pressure.

Drug therapy of type 1 hepatorenal syndrome Terlipressin (1 mg/4–6 h intravenous bolus) in combination with albumin should be considered the first line therapeutic agent for type 1 HRS. The aim of therapy is to improve renal function sufficiently to decrease serum creatinine to less than 133 mcmol/L (1.5 mg/dl) (complete response). If serum creatinine does not decrease at least 25% after 3 days, the dose of terlipressin should be increased in a stepwise manner up to a maximum of 2 mg/4 h. Median time to response is 14 days and usually depends on pre-treatment serum creatinine, the time being shorter in patients with lower baseline serum creatinine. A serum bilirubin less than 10 mg/dl before treatment and an increase in mean arterial pressure of >5 mm Hg at day 3 of treatment are associated with a high probability of response to therapy. For patients with partial response (serum creatinine does not decrease <133 mcmol/L) or in those patients without reduction of serum creatinine treatment should be discontinued within 14 days. Recurrence after withdrawal of therapy is uncommon and retreatment with terlipressin is generally effective.

In most studies, terlipressin was given in combination with albumin (1 g/kg on day 1 followed by 40 g/day) to improve the efficacy of treatment on circulatory function.

Japan Society of Transfusion Medicine and Cell Therapy: Evidence-based Guidelines for the Use of Albumin Products 2017

Hepatorenal syndrome is referred to as acute renal failure in patients with end-stage liver cirrhosis or hepatic insufficiency, such as fulminant hepatitis, but represents functional pre-renal failure without any organic or pathological changes in renal tissues. Hepatorenal syndrome is classified into 2 types: type 1 showing rapidly progressive symptoms of renal failure and type 2 showing slowly progressive renal failure. Patients with hepatorenal syndrome has a low glomerular filtration rate (serum Cr >1.5 mg/dl or 24-hour CCr <40 ml/min), resulting in oliguria. In many cases, hepatorenal syndrome progresses in an irreversible manner, is associated with a mortality rate of ≥90%, and is one of the causes of death in end-stage liver cirrhosis. The use of terlipressin and albumin is recommended for the treatment of type-1 hepatorenal syndrome. Improvement of renal impairment is also noted in 83% of patients with coadministration of norepinephrine and albumin, which represents a beneficial  treatment regimen while waiting for a liver transplant.

Treatment with a hypertonic albumin solution and a vasoconstrictor is effective in improving type-1 hepatorenal syndrome. Albumin should be administered at a dose of 1 g/kg body weight on day 1 and 20 to 40 g/body weight on subsequent days, in combination with terlipressin and other drugs (evidence grade 1A).

Guideline	Recommended Dosages of Human Albumin Injection for SBP
UptoDate [Accessed 19 August 2019]	Critically ill For at least two days as an intravenous bolus (1 g/kg per day [100 g maximum]) Not critically ill Given for two days as an intravenous bolus (1 g/kg/day [100 g maximum]), followed by 25-50 g/day until terlipressin therapy is discontinued
Clinical Guidelines for Human Albumin Use (NHS Scotland 2016)	Day 1          : 1 g/kg HAS Day 2 – 16  : 20 – 40 g HAS / day Rx continued until serum creatinine falls below 130mol/l. NB. Where creatinine is rising despite Rx, 60g HAS /day may be clinically indicated.
EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis 2010	1 g/kg on day 1, followed by 40 g/day
Evidence-based Guidelines for the Use of Albumin Products (Japan Society of Transfusion Medicine and Cell Therapy 2017)	1 g/kg body weight on day 1 , then, 20 to 40 g/body weight on subsequent days
Guideline for the use of human albumin solution (Guy’s and St. Thomas’ 2015)	Day 1: 1g/kg Day 2 -14: 0.5g/kg The transfusions should stopped once patient’s condition has resolved.
Guidelines for Intravenous Albumin Administration at Stanford Health Care (Stanford Health Care 2017)	Suspected HRS Defined as acute renal dysfunction (serum creatinine >1.5 mg/dL or 132.6 mcmol/L) in the presence of cirrhosis 1 g/kg/day for 2 days (max. 100 g/day) *
	Confirmed HRS Defined as: ·         Serum creatinine >1.5 mg/dL in the presence of cirrhosis ·         Absence of shock, ongoing bacterial infection, and/or current treatment with nephrotoxic drugs ·         Absence of sustained improvement in renal function after discontinuation of diuretics and a trial of albumin 1 g/kg ·         Absence of proteinuria (<500 mg/day) or hematuria (<50 red cells per high-power field) ·         Absence of ultrasonographic evidence of obstructive uropathy or parenchymal renal disease 25-50 g* daily for a total of 72 hours (starting 1-2 days after initial diagnostic trial of albumin, if applicable), and consult nephrology and hepatology services to determine whether to continue Should be used in addition to midodrine and octreotide
Albumin – Adult – Inpatient Clinical Practice Guideline (University of Wisconsin Hospitals 2018)	Management of hepatorenal syndrome (HRS) / acute kidney injury (AKI) in patients with cirrhosis and probable non-structural injury (i.e. pre-renal azotemia): As fluid challenge (UW Health low quality evidence; strong recommendation) Condition Albumin Type Dose Recommended Clinically volume depleted 5% Initial dose is 12.5 - 25 g Clinical volume repletion is achieved 25% 1 g/kg per day for 2 days * (max.100 g/day) Assess for resolution or progression of AKI at 48 hours after initiating albumin therapy
	Treatment of Type 1 HRS with cirrhosis (UW Health high quality evidence; strong recommendation) 1 g/kg on day 1 (max.100 g/day), then 25 g/day The following duration of therapy for albumin is recommended: 1.     For patients that respond to vasoconstrictors and albumin as evidenced by a decrease in plasma creatinine, discontinue albumin when plasma creatinine has returned to or is close to baseline, or has not decreased further after 3 days of treatment 2.     In patients that do not respond to vasoconstrictors and albumin, discontinue albumin after a maximum of 7 days 3.     Discontinue albumin if patient is started on renal replacement therapy or the plasma albumin level is > 3 g/dL (30 g/L).

*Use 25%.

References: UptoDate: Hepatorenal syndrome [Accessed 19 August 2019] NHS Services Scotland: National Plasma Products Expert Advisory Group. Clinical Guidelines for Human Albumin Use. Weinacker A & Ang H. Guidelines for Intravenous Albumin Administration at Stanford Health Care. 2017. Stanford Health Care. Retter et al. Guideline for the use of human albumin solution (HAS). 2015. Guy’s and St. Thomas’ NHS Foundation Trust. Fish et al.  Albumin – Adult – Inpatient Clinical Practice Guideline. 2018.  University of Wisconsin Hospitals and Clinics Authority European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. Journal of Hepatology 2010 vol. 53 j 397–417.

Human Albumin Injection in Spontaneous Bacterial Peritonitis (SBP)

UptoDate: Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis

Renal failure develops in 30 to 40 percent of patients with SBP and is a major cause of death. The risk may be decreased with an infusion of intravenous albumin (1.5 g per kg body weight within six hours of diagnosis and 1.0 g/kg body weight on day three). Albumin infusion should be given if the creatinine is >1 mg/dL (88 micromol/L), the blood urea nitrogen is >30 mg/dL (10.7 mmol/L), or the total bilirubin is >4 mg/dL (68 micromol/L). Once renal failure has developed, treatment with a combination of octreotide and midodrine may be helpful, in addition to infusion of 25 grams of 25 percent albumin daily, unless there is massive fluid overload.

The development of renal failure is associated with activation of the renin-angiotensin system and a decrease in effective arterial volume. Thus, it has been hypothesized that plasma volume expansion could attenuate the hemodynamic changes in patients with SBP, thereby preserving renal function and hence reduce mortality. A meta-analysis of four randomized trials (with a total of 288 patients) by Salerno et al. 2013 evaluated the impact of albumin infusion (in addition to antibiotics) on renal impairment and mortality in patients with SBP. Albumin infusion was associated with a significant decrease in the incidence of renal impairment (8 versus 31 percent) and a significant reduction in mortality (16 versus 35 percent).

EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis

A randomized, controlled study in patients with SBP treated with cefotaxime showed that albumin (1.5 g/kg body weight at diagnosis, followed by 1 g/kg on day 3) significantly decreased the incidence of type 1 HRS (from 30% to 10%) and reduced mortality from 29% to 10% compared with cefotaxime alone.

Treatment with albumin was particularly effective in patients with baseline serum bilirubin ≥68 mcmol/L (4 mg/dl) or serum creatinine ≥88 mcmol/L (1 mg/dl). It is unclear whether intravenous albumin is useful in patients with baseline bilirubin <68 mcmol/L and creatinine <88 mcmol/L, as the incidence of type 1 HRS was very low in the two treatment groups (7% without albumin and 0% with albumin).

It is not known whether crystalloids or artificial colloids could replace albumin in the prevention of HRS in patients with SBP. Albumin improves circulatory function in patients with SBP while equivalent doses of hydroxyethyl starch have no such beneficial effect.

Therefore, the EASL guidelines summarises that:

• ·         Hepatorenal syndrome (HRS) occurs in approximately 30% of patients with SBP treated with antibiotics alone, and is associated with a poor survival.
• ·         The administration of albumin (1.5 g/kg at diagnosis and 1g/kg on day 3) decreases the frequency of HRS and improves survival (Level A1).
• ·         It is unclear whether albumin is useful in the subgroup of patients with baseline serum bilirubin <68 mcmol/L and creatinine <88 mcmol/L (Level B2).
• ·         Until more information is available, we recommend that all patients who develop SBP should be treated with broad spectrum antibiotics and intravenous albumin (Level A2).

Guideline	Recommended Dosages of Human Albumin Injection for SBP
UptoDate [Accessed 19 August 2019]	1.5 g/kg body weight within six hours of diagnosis and 1.0 g/kg body weight on day three
Clinical Guidelines for Human Albumin Use (NHS Scotland 2016)	Day 1: 1.5g HAS / kg given over a 6 hour period: Day 3: 1g HAS / kg given over 3 hours (high risk of mortality defined as: urea ≥11 mmol/L and/or bilirubin ≥ 68 mcmol/L)
Guidelines for Intravenous Albumin Administration at Stanford Health Care (Stanford Health Care 2017)	1.5 g/kg within 6-hours of detection (day 1) and 1 g/kg on day 3 *
Albumin – Adult – Inpatient Clinical Practice Guideline (University of Wisconsin Hospitals 2018)	Dose: 1.5 g/kg on day 1, followed by 1 g/kg on day 3. Maximum daily dose: 100 g (400 mL) *
EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis 2010	1.5 g/kg at diagnosis and 1g/kg on day 3
Evidence-based Guidelines for the Use of Albumin Products (Japan Society of Transfusion Medicine and Cell Therapy 2017)	1.5 g per kilogram of body weight within 6 hours after diagnosis, followed by 1 g per kilogram of body weight on day 3 of illness
Guideline for the use of human albumin solution (Guy’s and St. Thomas’ 2015)	Day 1 and 2: 1.5g/kg Day 3 onwards: 1g/kg until significant improvement in the patients clinical condition

*Use 25%.

References:

1. UptoDate: Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis  [Accessed 19 August 2019]
2. NHS Services Scotland: National Plasma Products Expert Advisory Group. Clinical Guidelines for Human Albumin Use.
3. Weinacker A & Ang H. Guidelines for Intravenous Albumin Administration at Stanford Health Care. 2017. Stanford Health Care.
4. Retter et al. Guideline for the use of human albumin solution (HAS). 2015. Guy’s and St. Thomas’ NHS Foundation Trust.
5. Fish et al.  Albumin – Adult – Inpatient Clinical Practice Guideline. 2018.  University of Wisconsin Hospitals and Clinics Authority
6. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. Journal of Hepatology 2010 vol. 53 j 397–417.

Riamet & Rifampicin Co-administration

 [Pg 36]

Treatment of uncomplicated Plasmodium falciparum malaria

Factors associated with altered drug exposure and treatment response:

• Decreased exposure to lumefantrine has been documented in young children (<3 years)as well as pregnant women, large adults, patients taking mefloquine, rifampicin or efavirenz and in smokers. As these target populations may be at increased risk for treatment failure, their responses to treatment should be monitored more closely and their full adherence ensured.

[Pg 48]

Treatment of uncomplicated P.falciparum malaria in special populations

Several important patient sub-populations, including young children, pregnant women and patients taking potent enzyme inducers (e.g. rifampicin, efavirenz), have altered pharmacokinetics, resulting in sub-optimal exposure to antimalarial drugs. This increases the rate of treatment failure with current dosage regimens. The rates of treatment failure are substantially higher in hyperparasitaemic patients and patients in areas with artemisinin-resistant falciparum malaria, and these groups require greater exposure to antimalarial drugs (longer duration of therapeutic concentrations) than is achieved with current ACT dosage recommendations. It is often uncertain how best to achieve this. Options include increasing individual doses, changing the frequency or duration of dosing, or adding an additional antimalarial drug. Increasing individual doses may not, however, achieve the desired exposure (e.g. lumefantrine absorption becomes saturated), or the dose may be toxic due to transiently high plasma concentrations (piperaquine, mefloquine, amodiaquine, pyronaridine). An additional advantage of lengthening the duration of treatment (by giving a 5-day regimen) is that it provides additional exposure of the asexual cycle to the artemisinin component as well as augmenting exposure to the partner drug. The acceptability, tolerability, safety and effectiveness of augmented ACT regimens in these special circumstances should be evaluated urgently.

[Pg 56]

Treatment of uncomplicated P.falciparum malaria in special populations

5.5 | PATIENTS CO-INFECTED WITH TUBERCULOSIS

Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate. Similarly, concomitant rifampicin with mefloquine in healthy adults was associated with a there-fold decrease in exposure to mefloquine.

In adults co-infected with HIV and tuberculosis who were being treated with rifampicin, administration of artemether + lumefantrine resulted in significantly lower exposure to artemether, dihydroartemisinin and lumefantrine (nine-, six- and there-fold decreases, respectively). 

There is insufficient evidence at this time to change the current mg/kg bw dosing recommendations; however, as these patients are at higher risk of recrudescent infections they should be monitored closely.

[Pg 274-275]

Ref: WHO Guidelines for the Treatment of Malaria – 3rd Edition, 2015