The P-I-E-N-O Parkinsn's List Drug Database
venlafaxine / EffexorTM
ANTIDEPRESSANT:
(SNRI) : HIGH RISK
Description: Venlafaxine is an oral antidepressant agent that is structurally unrelated to other available antidepressants. It is indicated for the treatment of major depression. Venlafaxine appears to be effective in treating patients with melancholia, a severe form of depression. Its side effect profile is similar to that of the selective serotonin reuptake inhibitors (SSRIs). It should not be used in patients who are receiving or have recently received MAOI therapy. Venlafaxine was approved by the FDA in December 1993.
Mechanism of Action: Like the tricyclics, venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), exert their antidepressant effects by inhibiting the reuptake of both serotonin and norepinephrine. Both parent and metabolite also have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics, exert no in vitro activity at histaminergic, muscarinic, or ›A-adrenergic receptors, which accounts for its lack of anticholinergic, sedative, and cardiovascular side effects frequently observed with the tricyclic antidepressants. However, despite the claims of minimal muscarinic receptor activity, anticholinergic side effects may still occur with venlafaxine. Neither parent or metabolite possess monoamine oxidase inhibiting activity. Clinically, improvements in symptoms associated with both major depression and melancholia are observed. Pharmacokinetics: Venlafaxine is administered orally. It is well absorbed from the gastrointestinal tract, with food having no significant effect on venlafaxine absorption or the formation of its active metabolite, ODV. Time to peak concentrations can vary, but on average occur at approximately 2 and 4 hours for venlafaxine and ODV, respectively. Protein binding is approximately 27% for venlafaxine and 30% for ODV. Metabolism occurs hepatically, with elimination occurring primarily via the urine as unchanged drug, conjugated ODV, ODV, and inactive metabolites. The elimination half-lives of venlafaxine and ODV are 5 and 11 hours, respectively, and are affected by the presence of hepatic and/or renal disease.
For patients with cirrhosis, half-life of venlafaxine is increased by 30% and clearance decreased by 50%. The elimination of ODV in hepatically impaired patients is also affected; half-life increases by 60% and clearance decreases by 30%. Individual patients show considerable variability. Dosage adjustment is necessary in hepatically impaired patients.
For patients with renal impairment dosage adjustment is also necessary; venlafaxine half-life increases roughly 50% and clearance decreases roughly 24%. Similarly, ODV half-life increases by about 40%, but clearance appears to be unaffected. As with hepatic impairment, individual patients show variability.
CONTRAINDICATIONS/PRECAUTIONS: Venlafaxine is classified as pregnancy category C. Use of this agent in pregnant women should be undertaken only if clearly needed. Also, caution should be observed when administering this agent to breast-feeding women because it is unknown whether venlafaxine or its metabolites distribute into breast milk.
Administration of venlafaxine to patients with preexisting hepatic disease or renal impairment should be done cautiously because the drug is hepatically metabolized, and venlafaxine and its metabolites are renally eliminated.
Because venlafaxine is associated with a dose-related sustained hypertension, it should be used with caution in patients with preexisting hypertension. Blood pressure should be routinely monitored during therapy with venlafaxine.
Based on reports during use of venlafaxine, this drug may activate mania or hypomania. Venlafaxine should be used cautiously in patients with a history of mania.
In premarketing studies, venlafaxine was associated with a low incidence of seizures (0.26%). This agent should be used with caution in patients with a history of seizures. If seizures develop during therapy, use of venlafaxine should be terminated.
Venlafaxine produces a dose-dependent weight loss. About 5% of body weight was lost in 6% of patients, compared to 1% of patients receiving placebo. Anorexia occurred in 11% of patients, compared to 2% treated with placebo. Cautious use of venlafaxine in underweight depressed patients is recommended, especially those known to have anorexia nervosa.
All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy and venlafaxine prescribed in the smallest quantity consistent with good management.
DRUG INTERACTIONS: Coadministration of venlafaxine and cimetidine resulted in decreased first-pass effect of venlafaxine. Maximum concentrations of venlafaxine were increased and clearance reduced. At present, the manufacturer recommends no dosage adjustments in normal patients, but caution should be observed in the elderly and in patients with preexisting hypertension and/or hepatic disease or impairment because the results of this interaction can be more pronounced. O-desmethylvenlafaxine pharmacokinetics were not altered by cimetidine.
Venlafaxine as well as other antidepressants should not be used concurrently with monoamine oxidase inhibitors (MAOIs) such as furazolidone, pargyline, phenelzine, procarbazine, selegiline, or tranylcypromine. Concurrent use of venlafaxine with MAOIs has been associated with rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, and mental status changes that can include coma and delirium. This resembles neuroleptic malignant syndrome. An interval of 14 days is recommended between cessation of an MAOI and initiation of venlafaxine therapy. Also, at least 7 days should be allowed between cessation of venlafaxine therapy and the initiation of MAOI therapy. The manufacturer warns that venlafaxine should not be used in patients receiving MAOIs.
Information is not available on the concurrent use of venlafaxine with other CNS agents. Because of this, caution should be observed when administering venlafaxine with drugs that have CNS activity.
PATIENT INFORMATION:
What do venlafaxine tablets do?
Venlafaxine (EffexorTM ) is an antidepressant, a medicine that helps to lift mental depression. Venlafaxine can help patients whose depression has not responded to other medications, because it works in a different way. Generic venlafaxine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take venlafaxine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take venlafaxine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take venlafaxine tablets with food. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is less than two hours to your next dose, take only that dose and skip the missed dose. Do not take double or extra doses.
What other medicines can interact with venlafaxine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking venlafaxine?
Serious side effects with venlafaxine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with venlafaxine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take venlafaxine?
Visit your doctor for regular checks on your progress. You may have to take venlafaxine for 4 weeks before you feel better. If you have been taking venlafaxine for some time, do not suddenly stop taking it. You must gradually reduce the dose to avoid side effects. Ask your doctor for advice.
Venlafaxine can cause an increase in blood pressure. Check with your doctor; you may be able to measure your own blood pressure and pulse. Find out what your blood pressure and heart rate should be and when you should contact him or her.
You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how venlafaxine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.
Venlafaxine can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.
Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects.
If you are going to have surgery, tell your doctor or dentist that you are taking venlafaxine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at a controlled temperature between 20 and 25C (68 and 77F), in a dry place. Throw away any unused medicine after the expiration date.
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