VANCOMYCIN VALPROIC ACID THEOPHYLLINE PHENYTOIN

Available brand NOVO-VALPROIC NUELIN DILANTIN

Name Vancomycin Xellia 500 mg
powder for solution for
infusion.
Vancomycin Xellia 1000 mg
powder for solution for
infusion.

Class of Drug glycopeptide antibacterials Anticonvulsant agent Xanthine derivatives Anticonvulsant

Mechanism of Vancomycin is a tricyclic the mechanism of action of A methylxanthine derivative The primary site of action
Action glycopeptide antibiotic that valproic acid is unknown. from tea with diuretic, appears to be the motor
inhibits the synthesis of the The most popular theory is smooth muscle relaxant, cortex where spread of
cell wall in sensitive bacteria that valproic acid exerts its bronchial dilation, cardiac seizure activity is inhibited.
by binding with high affinity effects by increasing and central nervous system Possibly by promoting
to the D-alanyl-D-alanine the concentration of stimulant activities. sodium efflux from
terminus of cell wall precursor gamma-aminobutyric acid Mechanistically, neurons, phenytoin tends to
units. The drug is slowly (GABA) in the brain. theophylline acts as a stabilize the threshold
bactericidal for dividing phosphodiesterase inhibitor, against hyperexcitability
microorganisms. In addition, it adenosine receptor blocker, caused by excessive
impairs the permeability of the and histone deacetylase stimulation or
bacterial cell membrane and activator. environmental changes
RNA synthesis capable of reducing
membrane sodium gradient

Indication Complicated skin and soft -simple or complex relief and prophylaxis of Indicated for the control of
tissue infections absence seizures reversible bronchospasm generalized tonic-clonic
-Non necrotizing -primary generalized associated with asthma, and psychomotor (grand
- Necrotizing seizures with tonic-clonic chronic bronchitis and mal and temporal lobe)
Bone and joint infections manifestations. emphysema seizures and prevention and
Community-acquired treatment of seizures
pneumonia occurring during or
 Hospital-acquired pneumonia, following neurosurgery.
including ventilator-associated
pneumonia
Infective endocarditis

Acute bacterial meningitis

(For parenteral formulations
authorised

Doses and For adults (> 12yrs) capsule / 250 mg /day Adults: 13 mg/kg per 24hr. Adults: Patients who have
administration The recommended dose is 15 capsule / 500 mg/day Paediatric Population received no previous
(in all ages) to 20 mg/kg q 8 to 12 h (not to - administered orally. The Children over 2 years: treatment may be started on
exceed 2 g per dose). recommended initial Starting dose 16 mg/kg one 100 mg extended
In seriously ill patients, a dosage is 15 mg/kg/day, every 24 hours to a mean 20 phenytoin sodium capsule
loading dose of 25–30 mg/kg increasing at one-week mg/kg every 24 hours. three times daily, and the
. intervals by 5 to 10 Children under 2 years: Not dose then adjusted to suit
Infants and children (<12yr) mg/kg/day until seizures individual requirements
to be given except on the
The recommended dose is 10 are controlled. Pediatrics (< 18 years of
advice of a physician.
to 15 mg/kg ). - The maximal age): Initially, 5 mg/kg/day
vancomycin in neonates is: Children (from 6 months to in two or three equally
recommended dosage is 60
P D Interval mg/kg/day 16 years) have a more rapid divided doses, with
M o of clearance of theophylline subsequent dosage
A s administr resulting in the need for individualized to a
( e ation (h) higher per kg doses. maximum of 300 mg daily.
w (
e m
e g
k /
s k
) g
)
< 1 24
2 5
9
2 1 12
9 5
 -
3
5
> 1 8
3 5
5

Adjustment of Pregnancy When the total daily dose -Therapeutic serum levels Dosage should be
Doses Significantly increased doses exceeds 250 mg, it should are generally considered to individualized to provide
may be required to achieve be given in a divided be between 10 and 20 mg/L maximum benefit. In some
therapeutic serum regimen. A 500 mg enteric- (55 to 110 µmol/L). – cases, serum blood level
concentrations in pregnant coated capsule may be Dosage calculations should determinations may be
women . substituted for two 250 mg be based on lean body mass. necessary for optimal
Obese patients capsules. A serum level of 20 mg/L dosage adjustments. The
In obese patients, the initial (110 µmol/L) is an clinically effective serum
dose should be individually important reference point in level is usually 40-80
adapted according to total terms of toxicity micromol/L (10-20
body weight as in non-obese mcg/mL). Serum blood
patients. level determinations are
Adults especially helpful when
Dose adjustments in adult possible drug interactions
patients could be based on are suspected. With
glomerular filtration rate recommended dosage, a
estimated (eGFR) by the period of 7 to 10 days may
following formula: be required to achieve
Men: [Weight (kg) x 140 - age therapeutic blood levels
(years)]/ 72 x serum creatinine with DILANTIN and
(mg/dl) changes in dosage (increase
Women: 0.85 x value or decrease) should not be
calculated by the above carried out at intervals
formula shorter than 7 to 10 days.

Side Effects -sore throat, fever, chills -confusion, tiredness, cold Nausea/vomiting, stomach/ab headache, nausea,
 -hives feeling, vomiting, dominal vomiting, constipation,
-skin rash -easy bruising, unusual pain, headache, trouble dizziness, spinning
-itching bleeding (nose, mouth, or sleeping, diarrhea, irritability, sensation, drowsiness,
-difficulty breathing or - gums), restlessness, nervousness, slurred speech, loss of
swallowing -severe drowsiness; shaking, or increased balance or coordination,
-pain and muscle tightness of - chest pain, new or urination swollen or tender gums
the chest and back worsening cough with ,sleep problems (insomnia),
-unusual bleeding or bruising nervousness, tremors, or
fever, trouble breathing.
-blurred vision rash.

Contraindication - Hypersensitivity -hypersensitivity - Hypersensitivity

-Hypersensitivity - Bleeding disorders - currently suffer
- Pregnancy (cat D) from heart rhythm
- Liver dysfunction disorders
Warning & -Hypersensitivity reactions -tell your doctor if you are -Theophylline has a narrow - DILANTIN Capsules
Precautions -All patients receiving breast feeding. therapeutic index, the should not be abruptly
vancomycin should have -if you are having surgery, margin of safety above discontinued because of the
periodic haematologic studies, including dental surgery, therapeutic doses is small. possibility of increased
urine analysis, liver and renal tell the doctor or dentist -Whenever signs of seizure frequency,
function tests. that you are taking valproic intolerance to theophylline including status epilepticus.
-Vancomycin should be used acid. develop, the therapy should -Acute alcoholic intake
with caution in patients with may increase phenytoin
-valproic acid may make be reassessed.
allergic reactions to serum levels while chronic
you drowsy. Do not drive a -Theophylline clearance can
teicoplanin, since cross alcoholic use may decrease
hypersensitivity, including car or operate machinery be affected by various serum levels.
fatal anaphylactic shock, may until you know how this disease states, the age of -Phenytoin is not indicated
occur. medication affects you. the patient, concomitant for seizures due to
-Vancomycin has a spectrum -remember that alcohol use of other medication and hypoglycemic or other
of antibacterial activity limited can add to the drowsiness lifestyle habits metabolic causes.
to Gram-positive organisms. It caused by this medication -Use with caution in Appropriate diagnostic
is not suitable for use as a patients with severe cardiac procedures should be
single agent for the treatment disease, severe hypoxemia, performed as indicated.
of some types of infections hypertension, -In patients with renal or
unless the pathogen is already hyperthyroidism, cor hepatic impairment or in
 documented and known to be pulmonale, CHF , liver those with
susceptible or there is a high disease, in the elderly hypoalbuminemia, there is
suspicion that the most likely increased plasma levels of
pathogen(s) would be suitable unbound phenytoin. In
for treatment with patients with
vancomycin. hyperbilirubinemia, plasma
Ototoxicity, which may be levels of unbound
transitory or permennant phenytoin may also be
Vancomycin should also be elevated. Since unbound
avoided in patients with phenytoin concentrations
previous hearing loss. may be more useful in
Pain and thrombophlebitis these patient populations, it
may occur in many patients may affect dosing
receiving intravenous. considerations.

Over Dose In the event of renal -Overdosage with valproic -Overdose may cause The lethal dose of
insufficiency and colitis acid may result in anorexia, nausea, headache, phenytoin in adults is
accumulation may occur somnolence, heart block, irritability, agitation, estimated to be 2 to 5
resulting in high serum and deep coma. anxiety, insomnia, grams. The initial
concentrations. The incidence -Naloxone has been hypotension, palpitations symptoms are nystagmus,
of ototoxicity and reported to reverse the hyperthermia, ventricular ataxia, and dysarthria.
nefrotoxicity may be increased CNS depressant effects of arrhythmias, extreme thirst, Other signs are tremor,
in patients with increased
valproic acid overdosage delirium and convulsions. hyperreflexia, somnolence,
serum concentrations (>35
-Every theophylline drowsiness, lethargy,
g/ml one hour after infusion
or >10 g/ml directly before overdose should be slurred speech, blurred
infusion regarded as potentially fatal vision, nausea, vomiting.
and all patients should be The patient may become
closely monitored. comatose and hypotensive.
;There is no specific Bradycardia and
antidote to theophylline. asystole/cardiac arrest
Symptomatic support is have been reported
indicated e;gGastric lavage,
electrolyte balance
Important Drug amphotericin B, -valproic acid is highly aminoglutethimide, -Phenytoin is metabolized
Interactions aminoglycosides, bacitracin, protein bound and antibiotics, ephedrine, by hepatic cytochrome
 polymixin B, colistin, extensively metabolized by fluconazole, glucagon, (CYP) P450 enzymes
viomycin or cisplatin, when the liver, halothane, interferons, CYP2C9 and CYP2C19
indicated, requires careful -aspirin, which is also lithium, lomustine, and is particularly
monitoring. In such cases, the highly protein bound, can methotrexate, oral susceptible to inhibitory
dose of vancomycin must be displace valproate from its contraceptives or other drug interactions because it
decreased to a maximum of protein-binding sites and xanthine drugs; is subject to saturable
500 mg every 8 hours. precipitate toxicity. – • flu injections; metabolism. -
Concomitant administration of Serum levels of valproate Coadministration with
• medicines for alcoholism,
vancomycin and anaesthetics can be decreased drastically topiramate reduces serum
asthma, epilepsy, gout, CVS,
has been associated with in the presence of hepatic- topiramate levels by 59%,
erythema, histamine-like inducing agents. insomnia, stomach ulcers, and has the potential to
flushing, urticaria, and - Fluoxetine can increase • thiabendazole (a drug increase phenytoin levels
anaphylactic reactions. valproic acid used for killing worms, by 25% in some patients.
concentrations by inhibiting • viloxazine or selective -Molindone hydrochloride
liver metabolism. - serotonin re-uptake contains calcium ions
Valproate can drastically inhibitors, e.g., fluvoxamine which interfere with the
increase serum levels of (drugs used to treat absorption of phenytoin. -
lamotrigine and increase depression) Ingestion times of
the risk of life-threatening phenytoin and antacid
rash when administered calcium preparations,
concomitantly with including antacid
lamotrigine preparations containing
calcium should be
staggered to prevent
absorption problems.
Food Drug no no When immediate release It is therefore suggested
Interactions theophylline formulations that phenytoin not be
are administered with food, administered concomitantly
the rate of absorption is with an enteral feeding
reduced but absorption preparation.
remains complete.
ADRs Blood and the lymphatic signs of an allergic Gastrointestinal: Nausea, CNS: nystagmus, ataxia,
system disorders reaction (hives, difficult vomiting, epigastric pain,, slurred speech, decreased
Reversible neutropenia1, breathing, swelling in your diarrhea, anorexia, intestinal coordination, and mental
agranulocytosis, eosinophilia, face or throat) bleeding confusion.
thrombocytopenia, CNS: Headache, irritability, Gastrointestinal:
a severe skin
pancytopenia. reaction (fever, sore throat, restlessness, insomnia, vomiting, nausea,
Immune system disorders: burning eyes, skin pain, red twitching, convulsions and constipation.
Hypersensitivity reactions, or purple skin rash with reflex hyperexcitability. Hematopoietic:
anaphylactic reactions blistering and peeling). CVS: Palpitations, thrombocytopenia,
Ear and labyrinth disorders tachycardia, hypotension, leukopenia,
Transient or permanent loss circulatory failure, granulocytopenia, and
of hearing4 ventricular arrhythmias. pancytopenia with or
Vertigo, tinnitus3, Renal: Albuminuria, without bone marrow
dizziness diuresis and hematuria. suppression.
Renal and urinary Others: Hyperglycemia, Musculoskeletal System:
disorders: tachypnea and inappropriate Bone fractures and
Renal insufficiency manifested ADH syndrome osteomalacia have been
primarily by increased serum associated with chronic use
creatinine and serum urea of phenytoin.
Cardiac arrest