ADMELOG

The U.S. Food and Drug Administration (FDA) has approved Sanofi's
Admelog (insulin lispro) on Dec. 11, 2017.

ADMELOG is a rapid-acting human insulin analog indicated to improve

glycemic control in adults with type 2 diabetes and adults and children (3
years and older) with type 1 diabetes.
SORELLA 2 STUDY DESIGN: A 26-week, open-label, active-controlled study evaluated the
glucose lowering effect of ADMELOG plus insulin glargine, 100 Units/mL, compared to that of
Comparator (another insulin lispro product, 100 Units/mL, or a non–US-approved insulin lispro,
100 Units/mL), plus insulin glargine, 100 Units/mL. A total of 505 patients with T2DM treated
with insulin glargine 100 Units/mL and rapid-acting mealtime insulin analogs participated in the
study. Patients were randomized to ADMELOG (n=253) or Comparator (n=252). ADMELOG or
Comparator was administered by subcutaneous injection immediately prior to meals. The primary
endpoint was a change in AlC from baseline to week 26 (non-inferiority margin of 0.3%; Cl of
-0.209 to 0.091).
SORELLA 1 STUDY DESIGN: A 26-week, open-label, active-controlled study evaluated the
glucose lowering effect of ADMELOG plus insulin glargine, 100 Units/mL, compared to that of
Comparator (another insulin lispro product, 100 Units/mL, or a non–US-approved insulin lispro,
100 Units/mL), plus insulin glargine, 100 Units/mL. A total of 507 patients with T1DM treated
with insulin glargine 100 Units/mL and rapid-acting mealtime insulin analogs participated in the
study. Patients were randomized to ADMELOG (n=253) or Comparator (n=254). ADMELOG or
Comparator was administered by subcutaneous injection immediately prior to meals. The primary
endpoint was a change in AlC from baseline to week 26 (non-inferiority margin of 0.3%; Cl of
-0.086 to 0.20l).
Adverse Reactions
• Adverse reactions associated with ADMELOG include hypoglycemia, hypokalemia,
allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, weight gain, and
peripheral edema.

Contraindications
• ADMELOG is contraindicated during episodes of hypoglycemia and in patients with
hypersensitivity to insulin lispro or to any of its excipients.
PRICE
ADMELOG $99 - vial 10mL $149 - pack of 5 (3mL) pens
HUMALOG $174 $322
 Fiasp® (insulin aspart injection)
• On Sept. 29, 2017 Novo Nordisk announced that the U.S. FDA approved
Fiasp® (insulin aspart injection) 100 Units/mL, a fast-acting mealtime insulin
indicated to improve glycemic control in adults with type 1 and type 2
diabetes.
• Fiasp® can be dosed at the beginning of a meal or within 20 minutes after
starting a meal.
• It is a new formulation of NovoLog®, in which the addition of niacinamide
(vitamin B3) helps to increase the speed of the initial insulin absorption,
resulting in an onset of appearance in the blood in approximately 2.5 minutes.
• It will be available in a pre-filled delivery device FlexTouch ® pen and a 10
mL vial.
Onset of action: 20 minutes
Time to peak effect: 90 minutes
Duration of action: 5 hours

Side effects:
• Type 1 diabetes (mealtime; postmeal): nasopharyngitis (20.2%; 23.9%),
upper respiratory tract infection (9.1%; 7.4%), nausea (4.9%; 5.0%),
diarrhea (5.4%; 3.2%), and back pain (5.2%; 4.0%)
• Type 2 diabetes: urinary tract infection (5.9%)
CONTRAINDICATIONS
• During episodes of hypoglycemia.
• Hypersensitivity to insulin aspart or one of the excipients in FIASP.

ADVERSE REACTIONS
• Hypoglycemia, allergic reactions, hypersensitivity, injection site reactions,
lipodystrophy, and weight gain.

DRUG INTERACTIONS
• Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine)
• With TZD, may cause fluid retention and heart failure.
 RYSODEG
RYZODEG 70/30 (insulin degludec and insulin aspart injection)

RYZODEG 70/30 is a mixture of insulin degludec, a long-acting human

insulin analog, and insulin aspart, a rapid-acting human insulin analog,
indicated to improve glycemic control in patients 1 year of age and older with
diabetes mellitu
 TRESIBA
Brand Name: Tresiba
Generic Name: insulin degludec injection
On Sept 25, 2015, Novo Nordisk,announced that the U.S. FDA approved an
expanded indication for Tresiba®(insulin degludec injection 100 U/mL, 200
U/mL), a once-daily, long-acting basal insulin, to be used in children and
adolescents with diabetes.

Limitations of Use:
• Not recommended for treating diabetic ketoacidosis.
DOSAGE FORMS AND STRENGTHS:
• TRESIBA is available in the following package sizes:
• 100 units/mL (U-100): 3 mL FlexTouch®
• 200 units/mL (U-200): 3 mL FlexTouch®

CONTRAINDICATIONS
• During episodes of hypoglycemia and Hypersensitivity to TRESIBA or one of its
excipients .
ADVERSE REACTIONS
• Hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus,
rash, edema and weight gain.
DRUG INTERACTIONS
• Drugs that affect glucose metabolism: Adjustment of insulin dosage may be
needed; closely monitor blood glucose.
• Anti-Adrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and
reserpine): Signs and symptoms of hypoglycemia may be reduced or absent.
 Oral Insulin (ORMD-0801)
• Oramed Pharmaceuticals announced just recently that it is initiating a Phase IIb trial for its oral insulin

candidate ORMD-0801 capsule in 240 insulin-naïve patients with type II diabetes over 90 days with a

primary endpoint of HbA1c reduction.

• This will be the first clinical trial of its type for an oral insulin pill.

• There are two reasons this trial should be watched closely. First of all, obviously, to see if oral insulin can

lower 90-day blood sugar levels to below 7%.

• The endpoint is mean change in HbA1c from baseline to 12 weeks, but for any Phase III trial, HbA1c will

probably have to go below the 7% target to be approved.

• The second reason is to see the dosages required to lower HbA1c to that target.
• A previous Phase II trial used 16mg and 24mg doses as active comparators for
lowering pooled night time glucose.
• These doses are orders of magnitude higher than what is required for
injectable insulin, which is measured in IUs rather than milligrams.
• 1 IU of insulin is equivalent to 0.0347mg if human insulin, which means that
16mg is about 461 IUs.
• Patients start of insulin treatment with about half a unit per kilogram of body
weight per day.
• Assuming 80kg bodyweight, that’s 40 units a day, which means the 16mg
is about 10x as high in the amount of insulin required per dose.
• This makes sense given that much of the insulin is destroyed in the GI
tract.
• Biologics License Application (BLA) have been requested which would
grant a full 12 years of marketing exclusivity for ORMD-0801 if
approved. 
• On top of this, an additional six months of exclusivity can be granted if the
product also receives approval for use in pediatric patients.
 References
• https://www.clinicalleader.com/doc/first-oral-insulin-for-diabetics-takes-major-step-towards-fda-
approval-0001
• https://www.prnewswire.com/news-releases/oramed-announces-successful-meeting-with-fda-for-oral-
insulin-300513689.html
• http://www.diabetesincontrol.com/four-new-drugs-waiting-for-approval-that-can-change-the-diabetes-
landscape-part-2/
• http://products.sanofi.us/admelog/admelog.pdf
• https://www.admelogpro.com/
• http://press.novonordisk-us.com/2017-09-29-Novo-Nordisk-Receives-FDA-Approval-for-Fiasp-R-a-
New-Fast-Acting-Mealtime-Insulin
• https://www.novo-pi.com/fiasp.pdf
• http://press.novonordisk-us.com/2016-12-19-Novo-Nordisk-Receives-FDA-Approval-of-Tresiba-
insulin-degludec-injection-100-U-mL-200-U-mL-for-Use-in-Children-and-Adolescents-With-Diabetes
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203314lbl.pdf
 COLISTIN
• Colistin (also called polymyxin E) belongs to the polymyxin group of
antibiotics. It was first isolated in Japan in 1949 from Bacillus polymyxa
var. colistinus and became available for clinical use in 1959.
• Colistin was given as an intramuscular injection for the treatment of Gram-
negative infections, but fell out of favor after aminoglycosides became
available because of its significant side effects.
Mechanism of action:
• Colistin is available as both colistin sulfate and colistimethate sodium
(CMS). CMS is a prodrug that is hydrolyzed after intravenous
administration to produce the active drug colistin.
• Colistin is a bactericidal drug that binds to lipopolysaccharides and
phospholipids in the outer cell membrane of Gram-negative bacteria.
• It competitively displaces divalent cations from the phosphate groups of
membrane lipids, which leads to disruption of the outer cell membrane,
leakage of intracellular contents, and bacterial death .
• In addition to its bactericidal effect, colistin can bind and neutralize
lipopolysaccharide (LPS) and prevent the pathophysiologic effects of
endotoxin in the circulation.
Colistin has a narrow antibacterial spectrum and is primarily used for
infections with P. aeruginosa and A. baumannii.
SUSCEPTIBLE ORGANISMS:
Escherichia coli, Enterobacter spp., Haemophilus influenzae, Bordetella
pertussis, Legionella pneumophila, Klebsiella spp., Salmonella spp and
Shigella spp.
RESISTANT ORGANISMS:
Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus
spp., Providencia spp., and Morganella morganii.
Usual dosage:
2.5 to 5 mg/kg/day of Colistin base IM/IV in 2 to 4 divided doses,
depending on severity of infection.
Maximum dosage:
5 mg/kg/day of Colistin base.

- 1 mg colistin BASE activity = 2.4 mg colistimethate sodium

- 1 mg colistin BASE activity = 30,000 IU
- 1 mg colistimethate sodium (CMS) = 12,500 IU
 CL colistin Vd colistin
Greece Clcolistin = 8.2L/hr Vcolistin =218L
France Clcolistin=2.2L/hr Vcolistin=10.2L
ClHD(Colistin)=1.9L VHD(colistin)=28.3L
US and Thailand Clcolistin=2.72L/hr Vcolistin=45.1L
India Clcolistin=4.68L/hr Vcolistin=18L
INTRAVENOUS ADMINISTRATION
1. Direct Intermittent Administration—Slowly inject one-half of the total daily
dose over a period of 3 to 5 minutes every 12 hours.

2. Continuous Infusion—Slowly inject one-half of the total daily dose over 3

to 5 minutes. Add the remaining half of the total daily dose of Coly-Mycin M
Parenteral to NaCl, Dextrose, Ringer Lactate.
 Adverse effects
Renal Effects Neurologic Effects
Nephrotoxicity Ataxia
Dizziness
Respiratory Effects Neurotoxicity
Paresthesia
Apnea
Seizure
Respiratory distress
Slurred speech
Respiratory failure
Vertigo
Respiratory tract paralysis
Gastrointestinal Effects
Musculoskeletal Effects
Diarrhea
Neurological muscular paralysis
Gastrointestinal irritation
 MEROPENEM
• Meropenem is an injectable, broad spectrum, beta-lactum antibiotic used to treat infections in
critically ill patients.
• It is the second parenteral carbapenem to be introduced and has been in clinical use since 1994.
• It is active against gram-positive (ie, Enterococcus faecalis, Staphylococcus aureus,
Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-susceptible), Streptococcus
pyogenes, Viridans group streptococci), gram-negative bacteria (ie, Escherichia coli,
Haemophilus influenzae, Klebsiella pneumoniae, Neisseria meningitidis, Pseudomonas
aeruginosa, Proteus mirabilis), and anaerobic bacteria (ie, Bacteroides fragilis, Bacteroides
thetaiotaomicron, Peptostreptococcus species)
• It does not have activity against methicillin-resistant Staphylococcus aureus (MRSA)

or methicillin-resistant Staphylococcus epidermidis (MRSE).

• It continues to be an important option for empirical treatment of serious infections and

also considered as a last resort against ESBL producing bacilli in intensive care

settings.

• Meropenem exerts bactericidal activity by inhibiting cell wall synthesis by penetrating

the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-

binding–protein (PBP) targets.

 Indications
• Complicated skin and skin structure infections (adult patients and pediatric
patients 3 months of age and older only).
• Complicated intra-abdominal infections (adult and pediatric patients).
• Bacterial meningitis (pediatric patients 3 months of age and older only)
MERREM IV Dosage Schedule for Adult Patients with Renal Impairment
MERREM IV Dosage Schedule for Pediatric Patients 3 Months of Age
and Older with Normal Renal Function
MERREM IV Dosage Schedule for Pediatric Patients Less than 3 Months
of Age with Complicated Intra-abdominal Infections and Normal Renal
Function
 Pharmacokinetics
• Meropenem takes nearly 1 hour after the IV infusion to reach the maximum
plasma concentration.
• Protein bound portion of Meropenem is 2%.
• Volume of distribution – 12-20L.
• Metabolism - extra renal:20%-25% upto 50% if creatinine clearance less
than 20 mL/min.
• Excretion is renal, 70% unchanged. Total body clearance :188-300 mL/min
• Elimination half life is found to be 1hr in adults and children.
• Target steady-state concentrations (Css) between 8 and 16 mg/L have been
proposed.
 Adverse events
Most common: Diarrhoea (2.5%), Rash (1.4%) Nausea/vomiting (1.2%)
Other side effects:
Headache
Seizures
Anemia
Pain at injection site
GI bleeding