Effexor Xr (venlafaxine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Venlafaxine, a selective serotonin- and norepinephrine-reuptake inhibitor (SNRI), is a phenylethylamine-derivative antidepressant and anxiolytic agent.
Venlafaxine hydrochloride and venlafaxine besylate, selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), are phenylethylamine-derivative antidepressant and anxiolytic agents.
The exact mechanisms of antidepressant and anxiolytic actions of venlafaxine have not been fully elucidated but appear to be associated with the drug's potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. In vitro studies have demonstrated that venlafaxine and ODV do not possess any significant affinity for muscarinic cholinergic, H1-histaminergic, or alpha1-adrenergic receptors.
Venlafaxine and ODV exhibit linear kinetics over a dosage range of 75-450 mg per day; steady-state concentrations are attained within 3 days.
The absolute oral bioavailability of venlafaxine is about 45%. The time to achieve peak plasma concentrations of venlafaxine hydrochloride conventional tablets is 2 hours after administration; for venlafaxine hydrochloride extended-release formulations, the time to achieve peak plasma concentrations is 5.5 hours. Administration of venlafaxine hydrochloride with food does not affect the rate and extent of absorption of venlafaxine or ODV.
The time to achieve peak plasma concentrations of venlafaxine besylate extended-release tablets is 5-18 hours. Administration of venlafaxine besylate with a high-fat meal increases the mean peak plasma concentration of venlafaxine by 35% and by 22% for ODV. The median time to maximum concentration is also altered by food.
Venlafaxine is about 27% protein bound and ODV is about 30% protein bound. The elimination half-life is about 5 hours for venlafaxine hydrochloride and about 11 hours for ODV. For venlafaxine besylate extended-release tablets, the elimination half-life is about 6.8 hours for venlafaxine and 11.3 hours for ODV.
Venlafaxine is extensively metabolized, primarily to ODV, but also to other metabolites including N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. The cytochrome P-450 (CYP) isoenzyme 2D6 is involved in the formation of ODV. Venlafaxine is also metabolized via CYP3A, a minor pathway, to N-desmethylvenlafaxine, a minor metabolite.
Venlafaxine and its metabolites are principally excreted in the urine (87%). Pharmacokinetics of venlafaxine are not affected by age or sex.
Venlafaxine is commercially available in the US as venlafaxine hydrochloride and as venlafaxine besylate.
Generic name: venlafaxine HCl
Pronunciation: (ven-luh-FAX-een)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Effexor Xr:
- Anxiety With Depression
- Generalized Anxiety Disorder
- Major Depressive Disorder
- Panic Disorder
- Social Phobia
Also known as: Anxiety Associated With Depression, Major Unipolar Illness, Mixed Anxiety And Depressive Disorder, Panic Reaction, Panic-Like Sensation, Social Anxiety Disorder, Unipolar Mood Disorder.
Dosing
Dosages of venlafaxine hydrochloride and venlafaxine besylate are expressed in terms of venlafaxine.
Venlafaxine hydrochloride and venlafaxine besylate are administered orally.
Venlafaxine hydrochloride conventional tablets are administered in divided doses 2 or 3 times a day with food. Venlafaxine hydrochloride extended-release capsules and tablets and venlafaxine besylate extended-release tablets are administered once daily, either in the morning or in the evening at approximately the same time each day, with food. Food does not appear to affect GI absorption of venlafaxine hydrochloride. Ingestion of a high-fat meal when taken with venlafaxine besylate extended-release tablets increases plasma concentrations of venlafaxine and its metabolite.
The extended-release capsules and tablets of venlafaxine hydrochloride and venlafaxine besylate tablets should be swallowed whole with fluid and should not be divided, crushed, chewed, or placed in water.
The entire contents of venlafaxine hydrochloride extended-release capsules may be sprinkled on a small amount of applesauce immediately prior to administration; the patient should drink some water after swallowing the entire mixture without chewing to ensure that the pellets are completely swallowed.
Store venlafaxine hydrochloride conventional tablets, venlafaxine hydrochloride extended-release capsules, venlafaxine hydrochloride extended-release tablets, and venlafaxine besylate extended-release tablets at 20-25degreesC. Excursions are permitted between 15-30degreesC for venlafaxine hydrochloride extended-release tablets and venlafaxine besylate extended-release tablets. Protect venlafaxine hydrochloride extended-release tablets from moisture and humidity. Keep venlafaxine hydrochloride conventional tablets dry.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Venlafaxine is metabolized to its active metabolite O-desmethylvenlafaxine (ODV), principally by cytochrome P-450 (CYP) isoenzyme 2D6. Venlafaxine may also be metabolized to a minor metabolite by CYP3A4.
Venlafaxine is a weak inhibitor of CYP2D6.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to venlafaxine hydrochloride, venlafaxine besylate, desvenlafaxine succinate, or to any excipients in the formulation.
*Concurrent or recent (i.e., within 14 days) therapy with monoamine oxidase inhibitors (MAOIs), including linezolid and IV methylene blue.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse events reported in >=5% of patients receiving venlafaxine hydrochloride conventional tablets include asthenia, sweating, nausea, constipation, anorexia, vomiting, somnolence, dry mouth, dizziness, nervousness, anxiety, tremor and blurred vision, and abnormal ejaculation/orgasm and impotence in men.
Adverse events reported in >=5% of patients receiving venlafaxine hydrochloride extended-release capsules (Effexor XR(R)) include sweating, nausea, anorexia, somnolence, dry mouth, constipation, abnormal ejaculation, impotence in men, and libido decreased. The safety of venlafaxine besylate extended-release tablets is based on the extended-release capsules.
Adverse events reported in >=5% of patients receiving venlafaxine hydrochloride extended-release tablets for major depressive disorder include sweating, GI complaints (nausea, dry mouth, anorexia), CNS complaints (dizziness, somnolence, abnormal dreams), and abnormal ejaculation.
Adverse events reported in >=5% of patients receiving venlafaxine hydrochloride extended-release tablets for social anxiety disorder include asthenia, sweating, GI complaints (anorexia, dry mouth, nausea), CNS complaints (anxiety, insomnia, libido decreased, nervousness, somnolence, dizziness), abnormalities of sexual function (abnormal ejaculation, orgasmic dysfunction, impotence), yawning, and abnormal vision.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The safety and effectiveness of venlafaxine in pediatric patients have not been established; venlafaxine is not approved for use in pediatric patients. In 2 placebo-controlled trials in 766 pediatric patients with major depressive disorder and 2 placebo-controlled trials in 793 pediatric patients with generalized anxiety disorder, there were insufficient data to establish the safety and efficacy of venlafaxine for pediatric patients with these conditions. Additionally, studies with venlafaxine hydrochloride extended-release capsules suggest that their use in pediatric patients may adversely affect weight and height; decreases in appetite and weight loss have also been observed. Studies conducted in pediatric patients 6 to 17 years of age have found that blood pressure and cholesterol increases observed with venlafaxine are clinically relevant and similar to increases seen in adults.
An increased risk of suicidal thoughts and behaviors was observed in pediatric patients treated with antidepressants.
A National Pregnancy Registry for Antidepressants is available that monitors pregnancy outcomes in females exposed to antidepressants during pregnancy. Clinicians are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or by visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/antidepressants/.
Available epidemiologic data with venlafaxine in pregnant females have not established a drug-associated risk of major birth defects, miscarriage, or other adverse developmental outcomes.
Epidemiologic data found that exposure to SNRIs (including venlafaxine), particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage.
Observational studies have identified a potential increased risk for preeclampsia when venlafaxine is used during mid to late pregnancy. There are risks associated with untreated depression in pregnancy and poor neonatal adaptation in newborns with exposure to SNRIs during pregnancy.
In animal reproductive studies, no evidence of malformations or fetotoxicity was observed when venlafaxine was administered during the period of organogenesis at doses up to 2.5 or 4 times the maximum recommended human dose (MRHD) on a mg/m2 basis in rats and rabbits, respectively. However, an increase in postnatal mortality and decreased pup weights at 2.5 times the MRHD were observed with administration of venlafaxine to pregnant rats during gestation and lactation.
Neonates exposed to SNRIs late in the third trimester of pregnancy have developed complications requiring hospitalization, respiratory support, and tube feeding that can arise immediately upon delivery. Clinical findings reported to date in neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These clinical features appear to be consistent with either a direct toxic effect of the SNRI or possibly a drug withdrawal syndrome. It should be noted that, in some cases, the clinical picture was consistent with serotonin syndrome. Neonates exposed to venlafaxine during the third trimester of pregnancy should be monitored for discontinuation syndrome. When treating a pregnant female during the third trimester, carefully consider the potential risks and benefits of treatment.
Venlafaxine and its active metabolite are present in human milk and have not shown adverse reactions in breast-fed infants. It is not known if venlafaxine affects milk production. Consider the developmental and health benefits of breastfeeding, the mother's clinical need for the drug, and the potential for adverse effects on the breast-fed infant from exposure to venlafaxine or the underlying maternal condition.
No dosage adjustments are recommended for venlafaxine for geriatric patients based on age; caution should be exercised. Extra care should be taken when increasing and individualizing the dosage.
In clinical studies with venlafaxine hydrochloride extended-release tablets in major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder, there were 4, 6, 1, and 2% of patients who were >=65 years of age, respectively. In clinical studies with venlafaxine hydrochloride conventional tablets, 12% of patients were >=65 years of age.
Overall differences in efficacy and safety have not been observed between geriatric patients and younger patients. Geriatric patients may have greater sensitivity to medications and may also be at greater risk of developing hyponatremia.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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