The efficacy of venlafaxine hydrochloride extended-release capsules as a treatment for Panic Disorder (PD) was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for PD, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg per day in one study (study 1) and 75 or 225 mg per day in the other study (study 2).
Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full- symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two studies, venlafaxine hydrochloride extended-release capsule was statistically significantly more effective than placebo (for each fixed dose) on all three endpoints, but a dose-response relationship was not clearly established.
Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies.
In a longer term study (study 3), adult outpatients meeting DSM-IV criteria for PD who had responded during a 12-week open phase with venlafaxine hydrochloride extended-release capsules (75 to 225 mg per day) were randomly assigned to continue the same venlafaxine hydrochloride extended-release capsules dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions. Response during the open phase was defined as ≤ 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved). Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12 week open-label period, patients receiving continued venlafaxine hydrochloride extended-release capsules experienced a statistically significantly longer time to relapse.
a Odds ratio (drug to placebo) in terms of probability of free of full-symptom panic attacks based on logistic regression model.
95%CI: 95% confidence interval without adjusting for multiple dose arms.
* Doses statistically significantly superior to placebo.
|Study Number||Treatment Group||Primary Efficacy Measure: Whether Free of Full-symptom Panic Attacks|
|Percent of patients Free of Full symptom panic attack||Adjusted Odds Ratio a to placebo||Adjusted Odds Ratio a 95% Confidence Interval|
|Study 1||Ven XR 75 mg* Ven XR 150 mg* Placebo||54.1% (85/157) 61.4% (97/158) 34.4% (53/154)||2. 268 3.035 —||(1.43, 3.59) (1.91, 4.82) —|
|Study 2||Ven XR 75 mg* Ven XR 225 mg* Placebo||64.1% (100/156) 70% (112/160) 46.5% (73/157)||2.350 2.890 —||(1.46, 3.78) (1.80, 4.64) —|
Two placebo-controlled studies in 766 pediatric patients with MDD and two placebo-controlled studies in 793 pediatric patients with GAD have been conducted with venlafaxine hydrochloride extended-release capsules, and the data were not sufficient to support a claim for use in pediatric patients.
Venlafaxine Hydrochloride Extended-Release Capsules USP, 75 mg are white to off-white free flowing pellets filled in size 1 hard gelatin capsules with peach colored cap printed with ZA-36 in black ink & white body printed with “75 mg” in black ink and are supplied as follows:
NDC 68071-1728-9 BOTTLES OF 90
Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container.
Prescribers or other healthcare professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with venlafaxine hydrochloride extended-release capsules and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available for venlafaxine hydrochloride extended-release capsules. The prescriber or healthcare professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and should be asked to alert their prescriber if these occur while taking venlafaxine hydrochloride extended-release capsules.
Suicidal Thoughts and Behaviors
Advise patients, their families and caregivers to look for the emergence of suicidality, worsening of depression, and other psychiatric symptoms (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, psychomotor restlessness, hypomania, mania, other unusual changes in behavior), especially early during treatment and when the dose is adjusted up or down. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring [ see Boxed Warning and Warnings and Precautions ( 5.1) ].
Advise patients taking venlafaxine hydrochloride extended-release capsules not to use concomitantly other products containing venlafaxine or desvenlafaxine. Healthcare professionals should instruct patients not to take venlafaxine hydrochloride extended-release capsules with an MAOI or within 14 days of stopping an MAOI and to allow 7 days after stopping venlafaxine hydrochloride extended-release capsules before starting an MAOI [ see Contraindications ( 4.2) ].
Patients should be cautioned about the risk of serotonin syndrome, with the concomitant use of venlafaxine hydrochloride extended-release capsules and triptans, tramadol, amphetamines, tryptophan supplements, with antipsychotics or other dopamine antagonists, or other serotonergic agents [s ee Warnings and Precautions ( 5.2) and Drug Interactions ( 7.3) ].
Elevated Blood Pressure
Advise patients that they should have regular monitoring of blood pressure when taking venlafaxine hydrochloride extended-release capsules [ see Warnings and Precautions ( 5.3) ].
Patients should be cautioned about the concomitant use of venlafaxine hydrochloride extended-release capsules and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [ see Warnings and Precautions ( 5.4) ].
Angle Closure Glaucoma
Patients should be advised that taking venlafaxine hydrochloride extended-release capsules can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Preexisting glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see Warnings and Precautions ( 5.5)] .
Activation of Mania/Hypomania
Advise patients, their families and caregivers to observe for signs of activation of mania/hypomania [ see Warnings and Precautions ( 5.6) ].
Caution is advised in administering venlafaxine hydrochloride extended-release capsules to patients with cardiovascular, cerebrovascular, or lipid metabolism disorders [ see Adverse Reactions ( 6.1) ].
Serum Cholesterol and Triglyceride Elevation
Advise patients that elevations in total cholesterol, LDL and triglycerides may occur and that measurement of serum lipids may be considered [ see Warnings and Precautions ( 6.3) ].
Advise patients not to stop taking venlafaxine hydrochloride extended-release capsules without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping venlafaxine hydrochloride extended-release capsules [ see Warnings and Precautions ( 5.7) and Adverse Reactions ( 6.1) ].
Interference with Cognitive and Motor Performance
Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that venlafaxine hydrochloride extended-release capsules therapy does not adversely affect their ability to engage in such activities.
Advise patients to avoid alcohol while taking venlafaxine hydrochloride extended-release capsules [ see Drug Interactions ( 7.6) ].
Advise patients to notify their physician if they develop allergic phenomena such as rash, hives, swelling, or difficulty breathing.
Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy [ see Use in Specific Populations ( 8.1) ].
Advise patients to notify their physician if they are breast-feeding an infant [ see Use in Specific Populations ( 8.3) ].
Venlafaxine hydrochloride extended-release capsule contains spheroids, which release the drug slowly into the digestive tract. The insoluble portion of these spheroids is eliminated, and patients may notice spheroids passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids.
Medication Guide available at www.zydususa.com/medguides/ or call 1-877-993-8779.
Cadila Healthcare Ltd.
Zydus Pharmaceuticals (USA) Inc.
Pennington, NJ 08534
(ven” la fax’ een hye” droe klor’ ide)
Extended-Release Capsules, USP
Read the Medication Guide that comes with venlafaxine hydrochloride extended-release capsules before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.
What is the most important information I should know about venlafaxine hydrochloride extended-release capsules?
Venlafaxine hydrochloride extended-release capsules and other antidepressant medicines may cause serious side effects, including:
1. Suicidal thoughts or actions:
- Venlafaxine hydrochloride extended-release capsules and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed.
- Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
- Watch for these changes and call your healthcare provider right away if you notice:
- New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
- Pay particular attention to such changes when venlafaxine hydrochloride extended-release capsules are started or when the dose is changed.
Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:
- attempts to commit suicide
- acting on dangerous impulses
- acting aggressive or violent
- thoughts about suicide or dying
- new or worse depression
- new or worse anxiety or panic attacks
- feeling agitated, restless, angry or irritable
- trouble sleeping
- an increase in activity or talking more than what is normal for you
- other unusual changes in behavior or mood
- Visual problems
- eye pain
- changes in vision
- swelling or redness in or around the eye
Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Venlafaxine hydrochloride extended-release capsules may be associated with these serious side effects:
2. Serotonin Syndrome This condition can be life-threatening and may include:
- agitation, hallucinations, coma or other changes in mental status
- coordination problems or muscle twitching (overactive reflexes)
- racing heartbeat, high or low blood pressure
- sweating or fever
- nausea, vomiting, or diarrhea
- muscle rigidity
• increase your blood pressure. Control high blood pressure before starting
treatment and monitor blood pressure regularly
4. Enlarged pupils (mydriasis).
5. Anxiety and insomnia.
6. Changes in appetite or weight.
7. Manic/hypomanic episodes:
- greatly increased energy
- severe trouble sleeping
- racing thoughts
- reckless behavior
- unusually grand ideas
- excessive happiness or irritability
- talking more or faster than usual
Elderly people may be at greater risk for this. Symptoms may include:
- weakness or feeling unsteady
- confusion, problems concentrating or thinking or memory problems
10. Abnormal bleeding: Venlafaxine hydrochloride extended-release capsules and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin ® , Jantoven ®), a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin.
11. Elevated cholesterol.
12. Lung disease and pneumonia: Venlafaxine hydrochloride extended-release capsules may cause rare lung problems. Symptoms include:
- worsening shortness of breath
- chest discomfort
- trouble breathing
- swelling of the face, tongue, eyes or mouth
- rash, itchy welts (hives) or blisters, alone or with fever or joint pain.
Do not stop venlafaxine hydrochloride extended-release capsules without first talking to your healthcare provider. Stopping venlafaxine hydrochloride extended-release capsules too quickly or changing from another antidepressant too quickly may cause serious symptoms including:
- anxiety, irritability
- feeling tired, restless or problems sleeping
- headache, sweating, dizziness
- electric shock-like sensations, shaking, confusion, nightmares
- vomiting, nausea, diarrhea
Venlafaxine hydrochloride extended-release capsules are a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Venlafaxine hydrochloride extended-release capsules are also used to treat:
- Generalized Anxiety Disorder (GAD)
- Social Anxiety Disorder (SAD)
- Panic Disorder (PD)
Who should not take venlafaxine hydrochloride extended-release capsules?
Do not take venlafaxine hydrochloride extended-release capsules if you:
- are allergic to venlafaxine hydrochloride extended-release capsules or any of the ingredients in venlafaxine hydrochloride extended-release capsules. See the end of this Medication Guide for a complete list of ingredients in venlafaxine hydrochloride extended-release capsules.
- have uncontrolled angle-closure glaucoma
- take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
- Do not take an MAOI within 7 days of stopping venlafaxine hydrochloride extended-release capsules unless directed to do so by your physician.
- Do not start venlafaxine hydrochloride extended-release capsules if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.
People who take venlafaxine hydrochloride extended-release capsules close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:
- high fever
- uncontrolled muscle spasms
- stiff muscles
- rapid changes in heart rate or blood pressure
- loss of consciousness (pass out)
Before starting venlafaxine hydrochloride extended-release capsules, tell your healthcare provider if you:
- Are taking certain drugs such as:
- Medicines used to treat migraine headaches such as:
• Medicines used to treat mood, anxiety, psychotic or thought disorders, such as:
○ tricyclic antidepressants
○ antipsychotic drugs
• Medicines used to treat pain such as:
• Medicines used to thin your blood such as:
• Medicines used to treat heartburn such as:
• Over-the-counter medicines or supplements such as:
○ Aspirin or other NSAIDs
○ St. John’s Wort
- have heart problems
- have diabetes
- have liver problems
- have kidney problems
- have thyroid problems
- have or had seizures or convulsions
- have bipolar disorder or mania
- have low sodium levels in your blood
- have high blood pressure
- have high cholesterol
- have or had bleeding problems
- are pregnant or plan to become pregnant. It is not known if venlafaxine hydrochloride extended-release capsules will harm your unborn baby. Talk to your healthcare
- provider about the benefits and risks of
- treating depression during pregnancy
- are breast-feeding or plan to breast-feed. Some venlafaxine hydrochloride may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking venlafaxine hydrochloride extended-release capsules.
Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Venlafaxine hydrochloride extended-release capsules and some medicines may interact with each other, may not work as well, or may cause serious side effects.
Your healthcare provider or pharmacist can tell you if it is safe to take venlafaxine hydrochloride extended-release capsules with your other medicines. Do not start or stop any medicine while taking venlafaxine hydrochloride extended-release capsules without talking to your healthcare provider first.
|If you take venlafaxine hydrochloride extended-release capsules, you should not take any other medicines that contain (venlafaxine) including: venlafaxine hydrochloride.|
- Take venlafaxine hydrochloride extended-release capsules exactly as prescribed. Your healthcare provider may need to change the dose of venlafaxine hydrochloride extended-release capsules until it is the right dose for you.
- Venlafaxine hydrochloride extended-release capsules are to be taken with food.
- If you miss a dose of venlafaxine hydrochloride extended-release capsules, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of venlafaxine hydrochloride extended-release capsules at the same time.
- If you take too much venlafaxine hydrochloride extended-release capsules, call your healthcare provider or poison control center right away, or get emergency treatment.
- When switching from another antidepressant to venlafaxine hydrochloride extended-release capsules your doctor may want to lower the dose of the initial antidepressant first to avoid side effects
Venlafaxine hydrochloride extended-release capsules can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how venlafaxine hydrochloride extended-release capsule affects you. Do not drink alcohol while using venlafaxine hydrochloride extended-release capsules.
What are the possible side effects of venlafaxine hydrochloride extended-release capsules?
Venlafaxine hydrochloride extended-release capsules may cause serious side effects, including:
- See “What is the most important information I should know about venlafaxine hydrochloride extended-release capsules?”
- Increased cholesterol-have your cholesterol checked regularly
- Newborns whose mothers take venlafaxine hydrochloride extended-release capsules in the third trimester may have problems right after birth including:
- problems feeding and breathing
- shaking, jitteriness or constant crying
- Angle-closure glaucoma
- unusual dreams
- sexual problems
- loss of appetite, constipation, diarrhea, nausea or vomiting, or dry mouth
- feeling tired, fatigued or overly sleepy
- change in sleep habits, problems sleeping
- tremor or shaking
- dizziness, blurred vision
- feeling anxious, nervous or jittery
- increase in heart rate
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of venlafaxine hydrochloride extended-release capsules. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
How should I store venlafaxine hydrochloride extended-release capsules?
- Store at 68°F and 77°F (20°C to 25°C).
- Keep venlafaxine hydrochloride extended-release capsules in a dry place.
General information about venlafaxine hydrochloride extended-release capsules
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use venlafaxine hydrochloride extended-release capsules for a condition for which it was not prescribed. Do not give venlafaxine hydrochloride extended-release capsules to other people, even if they have the same condition. It may harm them.
This Medication Guide summarizes the most important information about venlafaxine hydrochloride extended-release capsules. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about venlafaxine hydrochloride extended-release capsules that is written for healthcare professionals.
Please address medical inquiries to MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779.
What are the ingredients in venlafaxine hydrochloride extended-release capsules?
Active ingredient: Venlafaxine hydrochloride, USP
Inactive ingredients: colloidal silicon dioxide, cetostearyl alcohol, gelatin, hypromellose, microcrystalline cellulose, polyacrylate dispersion, sodium lauryl sulfate, talc and titanium dioxide. Additionally each 37.5 mg capsule shell contains black iron oxide and each 75 mg and 150 mg capsule shell contains red iron oxide. The capsule is printed with black pharmaceutical ink which contains black iron oxide as coloring agent.
Medication Guide available at www.zydususa.com/medguides/ or call 1-877-993-8779.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
Cadila Healthcare Ltd.
Zydus Pharmaceuticals (USA) Inc.
Pennington, NJ 08534
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