Tuesday, March 31, 2020

Acetic Acid & Pseudomonas Aeruginosa

·         The concentrations effective for eliminating P. aeruginosa on small ulcerations and burns varied between 1 and 5%, and eradication occurred after 2–16 days .

·         On wounds, concentrations >2% caused pain and >5% caused a burning sensation.
Kramer, A., Dissemond, J., Kim, S., Willy, C., Mayer, D., Papke, R.,. Assadian, O. (2017). Consensus on Wound Antisepsis: Update 2018. Skin Pharmacology and Physiology,31(1), 28-58. doi:10.1159/000481545

·         Compresses with diluted acetic acid (0.5%–1%) can lower wound pH and create a hostile environment for Pseudomonas and other bacteria that prefer an alkaline environment.
Sibbald RG1Elliott JAVerma LBrandon APersaud RAyello EA. (2017) Update: Topical Antimicrobial Agents for Chronic Wounds. Adv Skin Wound Care.  Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28914678


·         Acetic acid with concentration of 1% has shown to be efficacious against wide range of bacteria as well as fungi, simultaneously accelerating wound healing.
·         Patients were treated for a variable period of 7–21 days with 1% acetic acid.
·         There was a decrease in wound size, surrounding inflammation and induration after treatment with acetic acid, suggestive of wound healing. There was a marked improvement in terms of discharge, odour and granulation tissue.
·          Apart from stinging sensation on application complained by few patients, there were no significant side effects of the use of acetic acid for dressings.
·         Infected skin grafting donor sites also showed a decrease in the amount of soakage after treatment with 1% acetic acid and healed spontaneously without the need of grafting.





Agrawal, K. S., Sarda, A. V., Shrotriya, R., Bachhav, M., Puri, V., & Nataraj, G. (2017). Acetic acid dressings: Finding the Holy Grail for infected wound management. Indian journal of plastic surgery : official publication of the Association of Plastic Surgeons of India50(3), 273–280. doi:10.4103/ijps.IJPS_245_16

·         When used as soaks, a concentration of 5 per cent was the most effective for eliminating P. aeruginosa from wounds; the organism was eliminated from two wounds within 2 days, 6 wounds within 5 days and 2 wounds within 7 days. The longest period for elimination was 14 days.
·          Acetic acid was less successful when used at 0.50%  in immersion baths, elimination of P. aeruginosa required between 2 and 17 days treatment.

Sloss, J. M., Cumberland, N., & Milner, S. M. (1993). Acetic acid used for the elimination of Pseudomonas aeruginosa from burn and soft tissue wounds. Journal of the Royal Army Medical Corps,139(2), 49-51. doi:10.1136/jramc-139-02-04

·         Acetic acid in 1% and 5% concentrations has been widely used in an attempt to reduce pH.
·         Application of sterile gauze swabs soaked in 1%-5% concentrations to ulcers and burn wounds has been used in different studies.10-14 
·         Topical application of acetic acid in a concentration of 5% to burn and soft tissue wounds has been found to be an effective treatment for P. aeruginosainfections.10-14 
·         A 0.5% acetic acid irrigation solution is effective in clearing P. aeruginosa from contaminated or infected wound beds.
·         Though not bactericidal, acetic acid creates an acidic environment unfavorable for growth of P. aeruginosa.15 
·         Thus, irrigation of wounds with acetic acid solution proved to be effective in clearing P. aeruginosa from wound beds.


Prepared by: Nur Nabiha R. [31.07.2019]

Friday, March 27, 2020

BETAFERON® and Product Details

Interferon beta-1b 250mcg (8MU) (BETAFERON®)
Name Of The Medicinal Product
Betaferon 250 microgram/ml, powder and solvent for solution for injection
Qualitative And Quantitative Composition
Betaferon contains 300 microgram (9.6 million IU) of recombinant interferon beta-1b per vial.
Recombinant interferon beta-1b* 250 microgram (8.0 million IU) per ml when reconstituted.
* produced by genetic engineering from a strain of Escherichia coli.
Therapeutic indications


1.       A single clinical event suggestive of multiple sclerosis(MS) (‘Clinically Isolated Syndrome’)
o  Indicated to delay progression to definite multiples sclerosis

2.       Relapsing forms of Multiple sclerosis
o  Indicated for the reduction of frequency and degree of severity of clinical relapses in ambulatory patients

3.       Secondary progressive multiple sclerosis with active disease, evidenced by relapses or pronounced neurological deterioration within the last two years
o  Indicated for the reduction of frequency and degree of severity of clinical relapses and slowing the progression of disease
Age limitation
12 years old and above
Dosage and administration
Adults / Children And Adolescent ≥ 12 years old
The recommended dose is 250 microgram (8.0 million IU), contained in 1 ml of the reconstituted solution, to be injected subcutaneously every other day (EOD)

Dose titration recommended at the start of the treatment
Initial: 0.0625 mg (2 million units [0.25 mL]) every other day; gradually increase dose by 0.0625 mg every 2 weeks to a target dose of 0.25 mg (8 million units [1 mL]) every other day. The titration period may be adjusted according to individual tolerability.

No randomised controlled trials have been conducted in < 18 years old. However, data from observational studies suggested that the safety profile in adolescents ≥ 12 years old receiving 250 mcg Betaferon SC EOD is similar to that seen in adults.

Only limited information available on Betaferon use for those below 12. Therefore, Betaferon should NOT be given to this age group.

Remark: If a dose is missed, administer as soon as remembered; do not administer on 2 consecutive days.
Time subsequent doses every 48 hours.
Reconstitution

To reconstitute lyophilised interferon beta-1b for injection:
·          Connect the vial adapter with the attached needle on the vial.
·          Connect the pre-filled syringe with solvent to the vial adapter and inject the 1.2 ml of the solvent (sodium chloride solution, 5.4 mg/ml (0.54% w/v) into the Betaferon vial.
·          Dissolve the powder completely without shaking.
·          After reconstitution, draw the required volume of medicine from the vial into the syringe
·          Remove the vial with the vial adapter from the pre-filled syringe before injection.

Kindly refer to Pg 58-61 in the following link for graphic and more details:

Kindly refer to the following Youtube video link:
Method Of Administration
For subcutaneous injection
·          Site for injection:
o    Outer surface of the arms
o    Abdomen (except 2-inch area around the navel)
o    Buttocks
o    Thighs
·          For very thin patient, ONLY use the thigh or outer surface of the arms.
·          Rotate injection site.
·          Do not inject into area where skin is bruised, infected or broken.
·          Patient should be well hydrated
Kindly refer to Pg 58-61 in the following link for graphic and more details:

Kindly refer to the following Youtube video link:
Adverse reactions
(based on physical product leaflet)


Very common
≥ 1 in 10 users
Common
≥ 1 in 100 users
Uncommon
≥ 1 in 1000 users
Unknown frequency
ž Lymphocytopenia
ž Neutropenia
ž Headache
ž Insomnia
ž Incoordination
ž Abdominal pain
ž Raised ALT > 5X baseline
ž Rash / Skin disorder
ž Myalgia / Hypertonia
ž Urinary urgency
ž Injection site reaction
ž Flu-like symptoms
ž Pain
ž Fever / Chills
ž Peripheral oodema
ž Asthenia (physical weakness)

ž Lymphadenopathy
ž Hypertension
ž Dyspneoa
ž Raised  AST > 5x baseline
ž Impotence
ž Menorrhagia
ž Injection site necrosis
ž Chest pain
ž Malaise
ž Nephrotic syndrome
ž Glomerulo-sclerosis
ž Anaemia
ž Thrombocytopenia
ž Leukopenia
ž Thrombotic microangiopathy
ž Anaphylaxis
ž Capillary leak syndrome
ž Thyroid disorder
ž Blood triglyceride increase
ž Weight increase / decrease
ž Anorexia
ž Bronchospasm
ž Tachycardia
ž Palpitation
ž Vasodilatation
ž Pulmonary arterial hypertension
ž Raised GGT
ž Blood bilirubin increased
ž Psychiatric adverse events
ž Confusion / Anxiety
ž Emotional liability
ž Arthralgia
ž Menstrual disorder
ž Menorrhagia
ž Sweating
Special warnings / Precautions for use

Anaphylaxis / hypersensitivity
Discontinue use
Drug-induced lupus erythematosus
Discontinue use
Flu-like symptoms
·    Analgesics and/or antipyretics on treatment days.
·    Improvement in symptoms occurs over time.
Hepatotoxicity
·    Use with caution in patients with concurrent exposure to other hepatotoxic drugs. Monitor liver function tests as clinically necessary. Consider discontinuation if serum transaminase levels increase significantly or are associated with clinical symptoms (eg, jaundice).
Injection site reactions
·    Reversible / Irreversible necrosis may occur with continued therapy; reactions generally arise within the first 4 months of therapy, but have occurred ≥1 year after initiation
·    Tend to improve over time.
·    Patient and/or caregiver competency in injection technique should be confirmed and periodically re-evaluated.
·    Do not inject into affected area until completely healed
·    If multiple lesions occur, discontinue use until they are fully healed.
Leukopenia
·    Recommend routine monitoring of complete blood counts with differentials.
·    Dose reduction may be required.
(Severe) Psychiatric adverse events
·    e.g. psychosis, mania, depression, suicidal behavior/ideation
·    Avoid use in severe psychiatric disorders
·    Use with caution in patients with a history of depression
·    Those exhibiting symptoms of depression should be closely monitored and discontinuation of therapy should be considered.
Thrombotic microangiopathy
·    e.g. Thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) (some fatal; some occur few years after therapy)
·    Monitor for new onset hypertension / thrombocytopenia / impaired renal function
·    Consider discontinuation of therapy and prompt treatment if confirmed TTP/HUS.

Cardiovascular disease
·    Use with caution in patients with preexisting cardiovascular disease.
·    Rare cases of new-onset cardiomyopathy and/or HF have been reported.
·    If HF worsens in the absence of another etiology, consider discontinuation of therapy.
·    American Heart Association 2016: Interferon may cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (strength:  moderate/major)
Thyroid dysfunction
·    Thyroid abnormalities may develop with use
·    May worsen pre-existing thyroid conditions.
·    Monitor thyroid function tests every 6 months or as clinically necessary.
           
Others:  Bone marrow suppression, pancreatitis, nephritic syndrome, seizure disorder
Contraindications

·          Patients with a history of hypersensitivity to natural or recombinant interferon beta, human albumin or to any of the excipients
·         Canadian labeling: Additional contraindication (not in US labeling): Pregnancy, decompensated liver disease (Betaseron, Extavia); current severe depression and/or suicidal ideation (Extavia)
Monitoring

·          Baseline: Thyroid function test, thyroglubulin, anti-thyroglobulin antibody, TSH receptor antibody, thyroid peroxidise antibody
·          Baseline: GAD antibody, anti-islet cell antibody, fasting C-peptide level, fasting plasma glucose
·          Liver function tests
·          Full blood count with differentials
·          Adverse drug reactions / Side effects:
v Neuropsychiatric side effects
v Nephrotic syndrome: early signs or symptoms, e.g. oedema, proteinuria and impaired renal function
v Thrombotic microangiopathy: new onset hypertension, thrombocytopenia, or impaired renal function
v Others: Flu-like symptoms, allergic or anaphylactic reactions, injection-site reactions, worsening of cardiac symptoms (in HF patients); and for sign/symptoms of depression
Drug interactions

·            No interaction studies have been performed
·            Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when Betaferon is administered in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance
Pregnancy

Contraindicated.
·          No long-term studies have been conducted.
·          Data from pregnancy registries and post-marketing experience (mostly during 1st trimester) suggest that frequencies of miscarriages and congenital abnormalities in their children were comparable to estimated background risk in the general population.
·          Spontaneous abortions have been reported in MS subjects in controlled clinical trials, with incidence rates not exceeding those in general population.
·          Reproduction studies with rhesus monkeys revealed maternal toxicity and an increased rate of abortion, resulting in prenatal mortality. No malformations have been observed in the surviving animals.
Women of Child-bearing Potential
Consultation recommended regarding the need for appropriate contraception measures.
Lactation
Betaferon can be used during breast-feeding.
·          Unknown if excreted into breastmilk.
·          Limited information available on the transfer of interferon beta-1b into breast milk, together with the chemical / physiological characteristics of interferon beta, suggests that levels of interferon beta-1b excreted in human milk are negligible.
·          No harmful effects on the breastfed newborn/infant are anticipated.
Pharmaceutical Particulars
Vial (with powder for solution for injection): Human albumin, Mannitol
Solvent (sodium chloride solution 5.4 mg/ml (0.54% w/v): Sodium chloride, Water for injection
Compatibility
This medicinal product must NOT be mixed with other medicinal products except for the supplied solvent
Shelf life
As packaged for sale
2 years, starting from the date of sterile filtration of the bulk solution
After reconstitution, immediate use is recommended. However, the in-use stability has been demonstrated for 3 hours at 2-8 °C.

Special precaution
Do not store above 25°C.
Do not freeze.

P/S: Dosing for COVID-19 in adults [based on most available literature]: 250 mcg EOD x 14 days ( total 7 doses )


References
1.        Product leaflet: Betaferon 25 mcg/ml Injection (Updated 18 July 2018)
2.        EPAR Product information : Betaferon [online]
3.        https://youtu.be/fRuS6wG__-w [Accessed 28 Mac 2020]
4.        UpToDate [online]: Drug information: Interferon beta-1b [Accessed 27 Mac 2020]
5.        Hoo G, et al. Interferon beta-1b (Betaferon) use for COVID-19 (Interim Guide v3.0). Tan Tock Seng Hospital, 13 Feb 2020.
6.        Hospital Kuala Lumpur: COVID-19 Drug Summary [Updated 20 Mac 2020]
7.        Sarawak General Hospital: COVID-19 Treatment & Drug Doses [Updated 23 Mac 2020]
Prepared by Mohd Zulhelmy ; Edited by JCK Ho [30.03.2020]