NAVIDOXINE

Dr. Ommia Ali

Marco Talaat Rizk

 NAVIDOXINE
Navidoxine consists of Meclizine Hydrochloride, Vitamin B6
(Pyridoxine Hydrochloride).
Uses
Navidoxine Tablet is used for the treatment, control, prevention, &
improvement of the following diseases, conditions and symptoms:
• Nausea, vomiting and dizzin ess caused by motion sickness
• Inadequate dietary intake
• Drug-induced deficiency
• Navidoxine Tablet may also be used for purposes not listed here.

Side effects
Some common side effects such as drowsiness, dry mouth, and
tiredness may occur. Meclizine has been shown to have fewer dry
mouth side effects than the traditional treatment for motion sickness,
transdermal scopolamine. A very serious allergic reaction to this drug
is unlikely, but immediate medical attention should be sought if it
occurs. Symptoms of a serious allergic reaction may include rash,
itching, swelling, severe dizziness, and trouble breathing.

Mechanism of action
Meclizine is an antagonist at H1 receptors. It possesses anticholinergic,
central nervous system depressant, and local anesthetic effects. Its
antiemetic and antivertigo effects are not fully understood, but its
central anticholinergic properties are partially responsible. The drug
depresses labyrinth excitability and vestibular stimulation, and it may
affect the medullary chemoreceptor trigger zone.[18] Meclizine also is
a dopamine antagonist at D1-like and D2-like receptors[citation
needed] but does not cause catalepsy[note 1] in mice, perhaps because
of its anticholinergic activity.
Chemistry
Meclizine is a first-generation antihistamine (nonselective H1
antagonist) of the piperazine class. It is structurally and
pharmacologically similar to buclizine, cyclizine, and hydroxyzine, but
has a shorter half-life of six hours compared to cyclizine and
hydroxyzine with about 20 hours (though half-life should not be
confused with duration). It is used as an antivertigo/antiemetic agent,
specifically in the prevention and treatment of nausea, vomiting, and
dizziness associated with motion sickness.[18] Meclizine is sometimes
combined with opioids, especially ones of the open-chain class like
methadone, dextropropoxyphene, and dipipanone. Similarly, Diconal
is a combination drug containing dipipanone and cyclizine.
Dosage Forms
Excipient information presented when available (limited, particularly
for generics); consult specific product labeling. [DSC] = Discontinued
product
Tablet, Oral, as hydrochloride:
Dramamine Less Drowsy: 25 mg [contains fd&c yellow #10 aluminum
lake]
Medi-Meclizine: 25 mg [DSC]
Travel-Ease: 25 mg [contains fd&c yellow #10 aluminum lake]
Pharmacology
Antihistamine that suppresses vestibular end-organ receptors and
inhibits activation of central cholinergic pathways (Oosterveld 1985)
Distribution
Vd: 7 L/kg (Wang 2012)
Metabolism
Hepatic to norchlorcyclizine (Wang 2012)
Excretion
Urine and feces as unchanged drug and metabolites (Wang 2012)
Onset of Action
~1 hour (Wang 2012)
Time to Peak
Plasma: 3.1 ± 1.4 hours (Wang 2011; Wang 2012)
Duration of Action
~24 hours (Wang 2012)
Half-Life Elimination
5.2 ± 0.8 hours (Wang 2011; Wang 2012)
Contraindications
Hypersensitivity to meclizine or any component of the formulation
Drug Interactions
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of
Anticholinergic Agents. Anticholinergic Agents may diminish the
therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic
Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant
effect of Alcohol (Ethyl). Monitor therapy
Pharmacodynamics
Meclizine works on the higher centres of the brain to reduce nausea,
vomiting, or vertigo. It is effective against nausea and vomiting arising
from many causes, including motion sickness and disorders affecting
the vestibular system. The onset of action of meclizine is about 1 hour,
with effects lasting between 8 to 24 hours.4 Meclizine is reported to
cause drowsiness due to its anticholinergic actions.5
Mechanism of action
Vomiting is a centrally regulated reflex mechanism that initiates from
the vomiting center and the chemoreceptor trigger zone (CTZ) located
in the medulla. Motion sickness is also regulated by CTZ. The blood-
brain barrier near the CTZ is relatively permeable to circulating
mediators and CTZ can transmit impulses to vomiting center located in
the brainstem. Different receptors responding to different factors,
including histamine, 5-HT, enkephalins, substance P, and dopamine,
are expressed along the brainstem to activate respective pathways and
contribute to the control of vomiting. Histamine H1 receptors are
expressed on the vestibular nuclei and nucleus of the solitary tract
(NTS) that are activated by motion sickness and stimuli from the
pharynx and stomach. When activated, H1 receptor signaling from
these nuclei is transmitted to the CTZ and vomiting centre.3
Toxicity
The oral and intraperitoneal LD50 in mouse are 1600 mg/kg and 625
mg/kg, respectively. The lowest published toxic dose (TDLo) in rats
via the oral route is 800 mg/kg.MSDS
Symptoms of overdose mainly involve CNS depression with
drowsiness, coma, and convulsions. Hypotension may also occur,
particularly in the elderly. In children, anticholinergic effects and CNS
stimulation, characterized by hallucinations, seizures, trouble sleeping,
are more likely to occur. In case of overdose, symptomatic and
supportive treatment is recommended. In case of recent ingestion,
induction of emesis or gastric lavage should be initiated to limit further
drug absorption. Although there is no known antidote to meclizine,
physostigmine may be useful to counteract the CNS anticholinergic
effects of meclizine.5
References
1. Dailymed."VERTICALM (MECLIZINE HYDROCHLORIDE)
TABLET [ALVA-AMCO PHARMACAL COMPANIES,
INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28,
2018).
2. Dailymed."MECLIZINE HYDROCHLORIDE: DailyMed
provides trustworthy information about marketed drugs in the United
States. DailyMed is the official provider of FDA label information
(package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed
August 28, 2018).
3. "meclizine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed
August 28, 2018).