1.EFFEXOR XR HISTORY
How was Effexor XR discovered?

Venlafaxine hydrochloride is a synthetic derivative of phenethylamine and a prescription antidepressant first introduced by Wyeth in 1993, and marketed under the trade name of Effexor XR for extended-release capsules.

Wyeth is a global leader in pharmaceuticals, consumer health care products, and animal health care products.

Wyeth Pharmaceuticals makes pharmaceuticals to treat cardiovascular, gastrointestinal, and infectious diseases, as well as cancer, women's health concerns, depression, vaccines and infectious disease hemophilia, immunology, and oncology. Wyeth is also a leader in the development of nutritionals. 

Note: World-drugs.net sells generic version of Effexor XR

2.EFFEXOR XR FACTS

Effexor XR is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. Effexor XR is known as one of the most activating or energizing of the newer antidepressants. While this can be helpful to some, as many depressed patients report feeling exhausted and unmotivated, to others it poses the risk of increased anxiety and agitation.

Effexor XR is an effective antidepressant for many persons; however, it seems to be especially effective for those with treatment-resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief.

In addition, a September 2004 Consumer Reports study ranked Effexor XR as the most effective among six commonly prescribed antidepressants. 

3.ABOUT EFFEXOR XR MEDICATION

Effexor XR is a bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor, but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor.

Serotonin norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders. They are also sometimes used to treat anxiety disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD) and chronic neuropathic pain.

They act upon two neurotransmitters in the brain that are known to play an important part in mood, namely, serotonin and norepinephrine. This can be contrasted with the more widely-used selective serotonin reuptake inhibitors (SSRIs), which act only on serotonin.

SNRIs were developed more recently than SSRIs, and there are relatively few of them. Their efficacy as well as their tolerability appears to be somewhat better than the SSRIs, owing to their compound effect. It is expected that most future antidepressants will probably work on multiple neurotransmitters, like the SNRIs and novel antidepressants such as bupropion

What is depression?

Depression is a medical illness, like diabetes or high blood pressure. People don't choose to be depressed. It's not because they're weak or "crazy." Depression affects more than 17 million people in the United States each year. It's twice as common in women as in men. Symptoms of depression include the following:

• Feeling sad most of the day, nearly every day, for 2 weeks or longer
• Loss of interest in things you used to enjoy
• Lack of energy
• Sleep and appetite disturbances
• Weight changes
• Feelings of hopelessness, helplessness and worthlessness
• Not being able to make decisions
• Thoughts of death and suicide

What causes depression?

The exact cause of depression is not known. Doctors think it may be caused by a chemical imbalance in the brain. The imbalance could be caused by your genes or by events in your life. Sometimes there aren't enough chemical messengers (called neurotransmitters) in the brain. Two primary messengers, called serotonin (say "seer-o-tone-in") and norepinephrine (say "nor-ep-in-ef-rin"), are responsible for your moods (how you feel).

Symptoms of Depression You feel miserable and sad. You feel exhausted a lot of the time with no energy. You feel as if even the smallest tasks are sometimes impossible. You seldom enjoy the things that you used to enjoy-you may be off sex or food or may 'comfort eat' to excess. You feel very anxious sometimes. You don't want to see people or are scared to be left alone. Social activity may feel hard or impossible. You find it difficult to think clearly. You feel like a failure and/or feel guilty a lot of the time. You feel a burden to others. You sometimes feel that life isn't worth living. You can see no future. There is a loss of hope. You feel all you've ever done is make mistakes and that's all that you ever will do. You feel irritable or angry more than usual. You feel you have no confidence. You spend a lot of time thinking about what has gone wrong, what will go wrong or what is wrong about yourself as a person. You may also feel guilty sometimes about being critical of others (or even thinking critically about them). You feel that life is unfair. You have difficulty sleeping or wake up very early in the morning and can't sleep again. You seem to dream all night long and sometimes have disturbing dreams. You feel that life has/is 'passing you by.' You may have physical aches and pains, which appear to have no physical cause, such as back pain.

What are antidepressants?

Antidepressants are medicines used to help people who have depression. Most people with depression get better with treatment with antidepressants.

How do antidepressants work?

Most antidepressants are believed to work by slowing the removal of certain chemicals from the brain. These chemicals are called neurotransmitters. Neurotransmitters are needed for normal brain function. Antidepressants help people with depression by making these natural chemicals more available to the brain.

How long will you have to take an antidepressant?

Antidepressants are typically taken for at least 4 to 6 months. In some cases, patients and their doctors may decide that antidepressants are needed for a longer time.

What are the different kinds of antidepressants?

Antidepressants are put into groups based on which chemicals in the brain they affect. There are many different kinds of antidepressants, including:

Selective serotonin reuptake inhibitors (SSRIs)

• citalopram
• escitalopram
• fluoxetine
• paroxetine
• sertraline

These medicines tend to have fewer side effects than other antidepressants. Some of the side effects that can be caused by SSRIs include dry mouth, nausea, nervousness, insomnia, sexual problems and headache. 

Tricyclics

• amitriptyline
• desipramine
• imipramine
• nortriptyline

Common side effects of Effexor XR caused by these medicines include dry mouth, blurred vision, constipation, difficulty urinating, worsening of glaucoma, impaired thinking and tiredness. These antidepressants can also affect a person's blood pressure and heart rate.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

• venlafaxine
• duloxetine
• desipramine
• milnacipran
• nefazodone

Some common side effects caused by these medicines include nausea and loss of appetite, anxiety and nervousness, headache, insomnia and tiredness. Dry mouth, constipation, weight loss, sexual problems, increased heart rate and increased cholesterol levels can also occur. 

Norepinephrine and dopamine reuptake inhibitors (NDRIs)

• bupropion

Some of the common side effects in people taking NDRIs include agitation, nausea, headache, loss of appetite and insomnia. It can also cause increase blood pressure in some people.

Combined reuptake inhibitors and receptor blockers

• trazodone
• nefazodone
• maprotiline
• mirtazpine

Common side effects of these medicines are drowsiness, dry mouth, nausea and dizziness. If you have liver problems, you should not take nefazodone. If you have seizures, you should not take maprotiline.

Monamine oxidase inhibitors (MAOIs)

• isocarboxazid
• phenelzine
• tranlcypromine
• MAOIs are used less commonly than the other antidepressants. They can have serious side effects, including weakness, dizziness, headaches and trembling. Taking an MAOI antidepressant while you're taking another antidepressant or certain over-the-counter medicines for colds and flu can cause a dangerous reaction. Your doctor will also tell you what foods and alcoholic beverages you should avoid while you are taking an MAOI. You should not take an MAOI unless you clearly understand what medications and foods to avoid. If you are taking an MAOI and your doctor wants you to start taking one of the other antidepressants, he or she will have you stop taking the MAOI for a while before you start the new medicine. This gives the MAOI time to clear out of your body.

How will my doctor choose an antidepressant for me?

Your doctor will probably think about the following 10 points when choosing an antidepressant medicine for you:

• If you were depressed before and a certain antidepressant worked well, that antidepressant might be the right choice of medicine for you again.
• If any of your brothers or sisters, parents, uncles or aunts had depression and a certain antidepressant worked well for them, that medicine might work for you too.
• The choice of an antidepressant depends on your health. If a certain antidepressant would have a bad effect on a health problem you have, that medicine wouldn't be the right choice for you.
• Antidepressants may cause side effects. The right medicine for you may be the one that gives you the fewest side effects.
• The choice of an antidepressant depends on how often you have to take it. The less often you have to take the medicine, the easier it is for you to take all the doses you need to treat your depression.
• Some antidepressants cost more than others. Your doctor will choose an antidepressant that works for you and that you can afford.
• Your doctor will want to choose a medicine he or she has experience prescribing.
• Your doctor will choose an antidepressant that will help you with symptoms like sleeplessness, anxiety and lack of energy.
• If you're taking other medicines, your doctor will consider how an antidepressant will work with these other medicines.
• Some antidepressants don't work well with certain foods. If your doctor gives you one of these antidepressants, he or she will let you know which foods you should stop eating.

Will antidepressants affect my other medicines?

Antidepressants can have an effect on many other medicines. If you're going to take an antidepressant, tell your doctor about all the other medicines you take, including over-the-counter medicines and herbal health products (such as St. John 's wort). Ask your doctor and pharmacist if any of your regular medicines can cause problems when combined with an antidepressant.  

4.EFFEXOR XR EFFECTIVENESS
When is Effexor XR best taken?

Effexor XR is extensively metabolized in the liver via the CYP2D6 isoenzyme to O-desmethylvenlafaxine, which is just as potent a serotonin-norepinephrine reuptake inhibitor as the parent compound, meaning that the differences in metabolism between extensive and poor metabolizers are not clinically important.

Steady-state concentrations of Effexor XR and its metabolite are attained in the blood within 3 days. Therapeutic effects are usually achieved within 3-4 weeks.

Prescribed doses of Effexor XR are typically in the range of 75-225 mg per day, but higher doses of Effexor XR are sometimes used for the treatment of severe or treatment-resistant depression. Because of its relatively short half-life of 5 hours, Effexor XR should be administered in divided dosages throughout the day. 

5. EFFEXOR XR EFFECTS ON SPECIAL POPULATION
(How do different people react to Effexor XR?)

Pregnancy

There are no adequate and well-controlled studies of Effexor XR in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

If Effexor XR is used until or shortly before birth, discontinuation effects in the newborn should be considered.

Labor and Delivery

The effect of Effexor XR (venlafaxine hydrochloride) on labor and delivery in humans is unknown.

Nursing Mothers

Effexor XR and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Effexor XR, a decision should be made whether to discontinue nursing or to discontinue Effexor XR, taking into account the importance of the drug to the mother.

Usage in Children

Safety and effectiveness in individuals below 18 years of age have not been established.

Geriatric Use

Of the 2,897 patients in Phase 2 and Phase 3 depression studies with Effexor XR, 12% (357) were 65 years of age or over. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. As with other antidepressants, several cases of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported, usually in the elderly.

The pharmacokinetics of Effexor XR and ODV are not substantially altered in the elderly. No dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction.

6.EFFEXOR XR EFFECTS ON MEDICAL CONDITIONS
(How does Effexor XR affect your existing condition/ailment?)

Age and Gender

A pharmacokinetic analysis of 404 Effexor XR treated patients from two studies involving both b.i.d. and t.i.d. regimens showed that dose-normalized through plasma levels of either Effexor XR or O-desmethylvenlafaxine (ODV) were unaltered due to age or gender differences. Dosage adjustment based upon the age or gender of a patient is generally not necessary.

Liver Disease

In 9 patients with hepatic cirrhosis, the pharmacokinetic disposition of both venlafaxine and ODV was significantly altered after oral administration of venlafaxine. Effexor XR elimination half-life was prolonged by about 30%, and clearance decreased by about 50% in cirrhotic patients compared to normal subjects. ODV elimination half-life was prolonged by about 60% and clearance decreased by about 30% in cirrhotic patients compared to normal subjects. A large degree of intersubject variability was noted. Three patients with more severe cirrhosis had a more substantial decrease in Effexor XR clearance (about 90%) compared to normal subjects.

Dosage adjustment is necessary in these patients.

Renal Disease

In a renal impairment study, Effexor XR elimination half-life after oral administration was prolonged by about 50% and clearance was reduced by about 24% in renally impaired patients (GFR=10-70 mL/min), compared to normal subjects. In dialysis patients, Effexor XR elimination half-life was prolonged by about 180% and clearance was reduced by about 57% compared to normal subjects. Similarly, ODV elimination half-life was prolonged by about 40% although clearance was unchanged in patients with renal impairment (GFR=10-70 mL/min) compared to normal subjects. In dialysis patients, ODV elimination half-life was prolonged by about 142% and clearance was reduced by about 56%, compared to normal subjects. A large degree of intersubject variability was noted.

Dosage adjustment is necessary in these patients.

7.OTHER/ALTERNATE USES OF EFFEXOR XR
(What else does Effexor XR treat?)

Effexor XR has also been found to reduce the severity of 'hot-flashes' in menopausal women.

8.ADVERSE/SIDE EFFECTS of EFFEXOR XR
What are the side effects of Effexor XR?

Body as a whole

Frequent : chest pain substernal, chills, fever, neck pain;

Infrequent : face edema, intentional injury, malaise, moniliasis, neck rigidity, pelvic pain, photosensitivity reaction, suicide attempt, withdrawal syndrome;

Rare : appendicitis, bacteremia, carcinoma, cellulitis. 

Cardiovascular system

Frequent : migraine, postural hypotension, tachycardia;

Infrequent : angina pectoris, arrhythmia, extrasystoles, hypotension, peripheral vascular disorder (mainly cold feet and/or cold hands), syncope, thrombophlebitis;

Rare : aortic aneurysm, arteritis, first-degree atrioventricular block, bigeminy, bradycardia, bundle branch block, capillary fragility, cerebral ischemia, coronary artery disease, congestive heart failure, heart arrest, cardiovascular disorder (mitral valve and circulatory disturbance), mucocutaneous hemorrhage, myocardial infarct, pallor.

Digestive system

Frequent : increased appetite;

Infrequent : bruxism, colitis, dysphagia, tongue edema, esophagitis, gastritis, gastroenteritis, gastrointestinal ulcer, gingivitis, glossitis, rectal hemorrhage, hemorrhoids, melena, oral moniliasis, stomatitis, mouth ulceration;

Rare : cheilitis, cholecystitis, cholelithiasis, esophageal spasms, duodenitis, hematemesis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, ileitis, jaundice, intestinal obstruction, parotitis, periodontitis, proctitis, increased salivation, soft stools, tongue discoloration.

Endocrine system

Rare: goiter, hyperthyroidism, hypothyroidism, thyroid nodule, thyroiditis.

Hemic and lymphatic system

Frequent : ecchymosis;

Infrequent: anemia, leukocytosis, leukopenia, lymphadenopathy, thrombocythemia, thrombocytopenia;

Rare: basophilia, bleeding time increased, cyanosis, eosinophilia, lymphocytosis, multiple myeloma, purpura.

Metabolic and nutritional

Frequent: edema, weight gain;

Infrequent: alkaline phosphatase increased, dehydration, hypercholesteremia, hyperglycemia, hyperlipemia, hypokalemia, SGOT increased, SGPT increased, thirst;

Rare: alcohol intolerance, bilirubinemia, BUN increased, creatinine increased, diabetes mellitus, glycosuria, gout, healing abnormal, hemochromatosis, hypercalcinuria, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocholesteremia, hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, uremia.

Musculoskeletal system

Frequent : arthralgia;

Infrequent : arthritis, arthrosis, bone pain, bone spurs, bursitis, leg cramps, myasthenia, tenosynovitis;

Rare : pathological fracture, myopathy, osteoporosis, osteosclerosis, plantar fasciitis, rheumatoid arthritis, tendon rupture.

Nervous system

Frequent : amnesia, confusion, depersonalization, hypesthesia, thinking abnormal, trismus, vertigo;

Infrequent: akathisia, apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia, hypotonia, incoordination, libido increased, manic reaction, myoclonus, neuralgia, neuropathy, psychosis, seizure, abnormal speech, stupor;

Rare: akinesia, alcohol abuse, aphasia, bradykinesia, buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss of consciousness, delusions, dementia, dystonia, facial paralysis, abnormal gait, Guillain-Barre Syndrome, hyperchlorhydria, hypokinesia, impulse control difficulties, neuritis, nystagmus, paranoid reaction, paresis, psychotic depression, reflexes decreased, reflexes increased, suicidal ideation, torticollis.

Respiratory system

Frequent : cough increased, dyspnea;

Infrequent : asthma, chest congestion, epistaxis, hyperventilation, laryngismus, laryngitis, pneumonia, voice alteration;

Rare : atelectasis, hemoptysis, hypoventilation, hypoxia, larynx edema, pleurisy, pulmonary embolus, sleep apnea.

Skin and appendages

Frequent : pruritus;

Infrequent : acne, alopecia, brittle nails, contact dermatitis, dry skin, eczema, skin hypertrophy, maculopapular rash, psoriasis, urticaria;

Rare : erythema nodosum, exfoliative dermatitis, lichenoid dermatitis, hair discoloration, skin discoloration, furunculosis, hirsutism, leukoderma, petechial rash, pustular rash, vesiculobullous rash, seborrhea, skin atrophy, skin striae.

Special senses

Frequent : abnormality of accommodation, mydriasis, taste perversion;

Infrequent : cataract, conjunctivitis, corneal lesion, diplopia, dry eyes, eye pain, hyperacusis, otitis media, parosmia, photophobia, taste loss, visual field defect;

Rare : blepharitis, chromatopsia, conjunctival edema, deafness, exophthalmos, glaucoma, retinal hemorrhage, subconjunctival hemorrhage, keratitis, labyrinthitis, miosis, papilledema, decreased pupillary reflex, otitis externa, scleritis, uveitis.

Urogenital system

Frequent : metrorrhagia, prostatic disorder (prostatitis and enlarged prostate), urination impaired, vaginitis ;

Infrequent : albuminuria, amenorrhea, cystitis, dysuria, hematuria, leukorrhea, menorrhagia, nocturia, bladder pain, breast pain, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, vaginal hemorrhage ;

Rare : abortion, anuria, breast discharge, breast engorgement, balanitis, breast enlargement, endometriosis, female lactation, fibrocystic breast, calcium crystalluria, cervicitis, orchitis, ovarian cyst, prolonged erection, gynecomastia (male), hypomenorrhea, kidney calculus, kidney pain, kidney function abnormal, mastitis, menopause, pyelonephritis, oliguria, salpingitis, urolithiasis, uterine hemorrhage, uterine spasm, vaginal dryness.