VENLAFAXINE XR
The safety of venlafaxine in human pregnancy has not been established.
Venlafaxine Hydrochloride Extended Release Tablets 75 mg
Venlafaxine is used to treat depression and can
improve mood and energy levels, as well as help restore
the spirit of everyday life. Venlafaxine is known as the
norepinephrine-serotonin reuptake inhibitor (SNRI) that
works by helping to restore the balance of certain natural
substances (serotonin and norepinephrine) in the brain.
Indications and Uses:
Treatment of depression including depression with
associated anxiety, anxiety or generalized anxiety
disorder including long-term treatment and social
anxiety disorder. Prevention of relapse and
recurrence of depression. Treatment of panic
disorder.
Dosage and Administration:
Recommended Starting Dose: 75 mg given once daily.
Patients not responding to the initial 75-mg/day dose may benefit from dose
increases to a maximum of 225 mg/day. While the recommended dose for
moderately depressed patients is up to 225 mg/day for immediate-release
venlafaxine, more severely depressed patients in 1 study responded to a mean
dose of 350 mg/day (range of 150-375 mg/day).
Patients with Renal Impairment: The total daily dose of venlafaxine must be
reduced by 25-50% for patients with renal impairment with a glomerular filtration
rate (GFR) of 10-70 mL/min.
The total daily dose of venlafaxine must be reduced by 50% in hemodialysis
patients. Administration must be withheld until the dialysis session is completed.
Contraindications:
Hypersensitivity to venlafaxine or any other component of Efexor XR. Concomitant
use of venlafaxine and any monoamine oxidase inhibitors (MAOIs).
Venlafaxine must not be initiated for at least 14 days after discontinuation of
treatment with a MAOI; a shorter interval may be justified in the case of a reversible
MAOI. Venlafaxine must be discontinued for at least 7 days before starting
treatment with any MAOI (see Interactions).
Interactions:
Monoamine Oxidase Inhibitors (MAOIs): Severe adverse reactions have been
reported in patients who have recently been discontinued from a MAOI and started
on venlafaxine, or have recently had venlafaxine therapy discontinued prior to
initiation of a MAOI (see Contraindications). These reactions have included tremor,
myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with
features resembling neuroleptic malignant syndrome, seizures and death.
CNS-Active Drugs: Based on the known mechanism of action of venlafaxine and
the potential for serotonin syndrome, caution is advised when venlafaxine is co-
administered with other drugs that may affect the serotonergic neurotransmitter
systems [eg, triptans, selective serotonin re-uptake inhibitors (SSRIs), lithium].
Adverse Reactions:
Frequency of observed adverse reactions: Common: ≥ 1%; uncommon: ≥ 0.1%
and <1%; rare: ≥0.01% and <0.1%; very rare: <0.01%.
Cardiovascular: Common: Hypertension, vasodilatation (mostly hot
flashes/flushes). Uncommon: Hypotension, postural hypotension, syncope,
tachycardia. Very Rare: QT prolongation, ventricular fibrillation, ventricular
tachycardia (including Torsade de pointes).
Digestive: Common: Decreased appetite, constipation, nausea, vomiting.
Uncommon: Bruxism, diarrhea. Very Rare: Pancreatitis.
Waring and Precaution:
During treatment with these types of medication it is important that you and your
doctor have good ongoing communication about how you are feeling.
EFFEXOR XR is not for use in children under 18 years of age.
Use In Pregnancy & Lactation:
Pharmacokinetics: At least 92% of a single oral dose of venlafaxine is absorbed.
After administration of Efexor XR, the peak plasma concentrations of venlafaxine
Venlafaxine must be administered to pregnant women only if the expected benefits and ODV are attained within 6±1.5 and 8.8±2.2 hrs, respectively. The rate of
outweigh any possible risk. If venlafaxine is used until or shortly before birth, absorption of venlafaxine from the Efexor XR capsules is slower than its rate of
discontinuation effects in the newborn should be considered. Neonates exposed to elimination. Therefore, the apparent elimination half-life of venlafaxine following
venlafaxine late in the 3rd trimester have developed complications requiring administration of Efexor XR capsules (15±6 hrs) is actually the absorption half-life
respiratory support or prolonged hospitalization. instead of the true disposition half-life (5±2 hrs) observed following administration of
Venlafaxine and ODV are excreted in human milk; therefore, the use of Efexor XR in an immediate-release tablet.
nursing women cannot be recommended. When equal daily doses of venlafaxine were administered as either the immediate-
release tablet or the extended-release capsule, the exposure [area under the
Preg Safety: Category C: Either studies in animals have concentration curve (AUC)] to both venlafaxine and ODV was similar for the 2
revealed adverse effects on the foetus treatments, and the fluctuation in plasma concentrations was slightly lower
(teratogenic or embryocidal or other) and there following treatment with the Efexor XR capsule. Therefore, the Efexor XR capsule
are no controlled studies in women or studies provides a slower rate of absorption, but the same extent of absorption (ie, AUC), as
women and animals are not available. Drugs should be given only if the potential the Efexor immediate-release tablet.
benefit justifies the potential risk to the foetus. Venlafaxine undergoes extensive first-pass metabolism in the liver, primarily by
CYP2D6 to the major metabolite ODV. Venlafaxine is also metabolized to N-
Overdosage: desmethylvenlafaxine, catalyzed by CYP3A3/4 and other minor metabolites.
In post-marketing experience, overdose with venlafaxine was reported Venlafaxine and its metabolites are excreted primarily through the kidneys.
predominantly in combination with alcohol and/or other drugs. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hrs as
Electrocardiographic changes (eg, prolongation of QT interval, bundle branch either unchanged venlafaxine, unconjugated ODV, conjugated ODV or other minor
block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, metabolites.
hypotension, vertigo, disturbances of consciousness (ranging from somnolence to Administration of Efexor XR with food has no effect on the absorption of venlafaxine
coma), seizures and death have been reported. or on the subsequent formation of ODV. Subject age and sex do not significantly
Treatment: General supportive and symptomatic measures are recommended; affect the pharmacokinetics of venlafaxine. No accumulation of venlafaxine or ODV
cardiac rhythm and vital signs must be monitored. has been observed during chronic administration in healthy subjects.
When there is a risk of aspiration, induction of emesis is not recommended. Other Information: The extended-release formulation of venlafaxine contains
Gastric lavage may be indicated if performed soon after ingestion or in symptomatic spheroids, which release the drug slowly into the digestive tract. The insoluble
patients. Administration of activated charcoal may also limit drug absorption. portion of these spheroids is eliminated and may be seen in stools.
Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to
be of benefit. Toxicology:
No specific antidotes for venlafaxine are known. Preclinical Safety Data: Studies with venlafaxine in rats and mice revealed no
evidence of carcinogenesis. Venlafaxine was not mutagenic in a wide range of in
vitro and in vivo tests.
Mechanism of Action Reduced fertility was observed in a study in which both male and female rats were
Pharmacology: Venlafaxine and its active metabolite, O-desmethylvenlafaxine exposed to the major metabolite of venlafaxine (ODV). This ODV exposure was
(ODV), are potent inhibitors of serotonin and norepinephrine re-uptake, and weak approximately 2-3 times that of a human dose of 225 mg/day. The human relevance
inhibitors of dopamine re-uptake. The antidepressant activity of venlafaxine is of this finding is unknown.
thought to be associated with potentiation of neurotransmitter activity in the central
nervous system (CNS). Venlafaxine and ODV have no significant affinity for
muscarinic, histaminergic or α1-adrenergic receptors in vitro. Activity at these
receptors is potentially associated with various anticholinergic, sedative and
cardiovascular effects seen with other psychotropic drugs. In preclinical rodent
models, venlafaxine demonstrated activity predictive of antidepressant and
anxiolytic actions, and cognitive enhancing properties.
Pharmacodynamics: Depression: The efficacy of venlafaxine extended-release
capsules as a treatment for depression, including depression with associated
anxiety, was established in 2 placebo-controlled, short-term studies. Populations in
both trials consisted of outpatients meeting DSM III-R or DSM-IV criteria for major
depression.
The 1st study compared extended-release venlafaxine 75-150 mg/day, immediate-
release venlafaxine 75-150 mg/day and placebo for 12 weeks. Extended-release
venlafaxine showed significant advantage over placebo starting at week 2 of
treatment on the Hamilton Rating Score for Depression (HAM-D) total and HAM-D
depressed mood item, at week 3 on the Montgomery-Asberg Depression Rating
Scale (MADRS) total, and at week 4 on the Clinical Global Impressions (CGI)
severity of illness scale. All advantages were maintained through the end of the
treatment. Extended-release venlafaxine also showed significant advantage over
immediate-release venlafaxine at weeks 8 and 12 on the HAM-D total and CGI
severity of illness scale and at week 12 for all efficacy variables.
Social Anxiety Disorder (Social Phobia): The efficacy of Efexor XR as a treatment
for social anxiety disorder (also known as social phobia) was established in 2
double-blind, parallel group, 12-week multicenter, placebo-controlled, flexible-dose
studies in adult outpatients meeting DSM-IV criteria for social anxiety disorder.
Patients received doses in a range of 75-225 mg/day. Efficacy was assessed with
the Liebowitz Social Anxiety Scale (LSAS). In these 2 trials, Efexor XR was
significantly more effective than placebo on change from baseline to endpoint on
the LSAS total score.
Cost Effectiveness:

DEPRESSION
IS NEVER
SIMPLE

Reference:
Anonim, 2015. MIMS Indonesia. Online. AVAILABLE NOW:
http://www.mims.com/indonesia/drug/info/efexor%20xr/?type=full#Actio
ns. Diakses tanggal 17 November 2017.
VENLAFAXINE EXTENDED RELEASE TABLETS
Sonmez, I., & Kosger, F. (2015). Venlafaxine-Induced Acute Dystonia: a Case OFFER NEW ALTERNATIVE FOR TREATING
Report/Venlafaksin kullanimina bagli akut distoni: Olgu sunumu.
Dusunen Adam, 28(4), 374. MAJOR DEPRESSIVE DISORDER (MDD)
Van Baardewijk, M., Vis, P. M. J., & Einarson, T. R. (2005). Cost effectiveness of
duloxetine compared with venlafaxine‐XR in the treatment of major Venlafaxine Hydrochloride Extended Release
depressive disorder. Current medical research and opinion, 21(8),
1271-1279.

VENLAFAXINE 75 mg
XR Venlafaxine Hydrochloride
Extended-Release Tablets

PT. CORO INT