Venlafaxine Hydrochloride (Page 5 of 15)

5.12 Interstitial Lung Disease and Eosinophilic Pneumonia

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported. The possibility of these adverse events should be considered in venlafaxine-treated patients who present with progressive dyspnea, cough or chest discomfort. Such patients should undergo a prompt medical evaluation, and discontinuation of venlafaxine therapy should be considered.

5.13 Sexual Dysfunction

​ Use of SNRIs, including venlafaxine hydrochloride extended-release capsules, may cause symptoms of sexual dysfunction [see Adverse Reactions ( 6.1)]. In male patients, SNRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SNRI use may result in decreased libido and delayed or absent orgasm.
It is important for prescribers to inquire about sexual function prior to initiation of venlafaxine hydrochloride extended-release capsules and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:
• Hypersensitivity [see Contraindications ( 4.1)]
• Suicidal Thoughts and Behaviors in Children, Adolescents, and Adults [see Warnings and Precautions ( 5.1)]
• Serotonin Syndrome [see Warnings and Precautions ( 5.2)]
• Elevations in Blood Pressure [see Warnings and Precautions ( 5.3)]
• Abnormal Bleeding [see Warnings and Precautions ( 5.4)]
• Angle Closure Glaucoma [see Warnings and Precautions ( 5.5)]
• Activation of Mania/Hypomania [see Warnings and Precautions ( 5.6)]
• Discontinuation Syndrome [see Warnings and Precautions ( 5.7)]
• Seizure [see Warnings and Precautions ( 5.8)]
• Hyponatremia [see Warnings and Precautions ( 5.9)]
• Weight and Height changes in Pediatric Patients [see Warnings and Precautions ( 5.10)]
• Appetite Changes in Pediatric Patients [see Warnings and Precautions ( 5.11)]
• Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions ( 5.12)]

• Sexual Dysfunction [see Warnings and Precautions ( 5.13)]

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Most Common Adverse Reactions
The most commonly observed adverse reactions in the clinical study database in venlafaxine hydrochloride extended-release capsules treated patients in MDD, GAD, SAD, and PD (incidence ≥ 5% and at least twice the rate of placebo) were: nausea (30%), somnolence (15.3%), dry mouth (14.8%), sweating (11.4%), abnormal ejaculation (9.9%), anorexia (9.8%), constipation (9.3%), impotence (5.3%) and decreased libido (5.1%).
Adverse Reactions Reported as Reasons for Discontinuation of Treatment
Combined across short-term, placebo-controlled premarketing studies for all indications, 12% of the 3,558 patients who received venlafaxine hydrochloride extended-release capsules (37.5 to 225 mg) discontinued treatment due to an adverse experience, compared with 4% of the 2,197 placebo-treated patients in those studies.
The most common adverse reactions leading to discontinuation in ≥ 1% of the venlafaxine hydrochloride extended-release capsules treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7. Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration)

Body System Adverse Reaction	Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558	Placebo n = 2,197
Body as a whole
Asthenia	1.7	0.5
Headache	1.5	0.8
Digestive system
Nausea	4.3	0.4
Nervous system
Dizziness	2.2	0.8
Insomnia	2.1	0.6
Somnolence	1.7	0.3
Skin and appendages	1.5	0.6
Sweating	1	0.2

Common Adverse Reactions in Placebo-controlled Studies
The number of patients receiving multiple doses of venlafaxine hydrochloride extended- release capsules during the premarketing assessment for each approved indication is shown in Table 8. The conditions and duration of exposure to venlafaxine in all development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (venlafaxine hydrochloride only) and outpatient studies, fixed-dose, and titration studies. Table 8: Patients Receiving Venlafaxine Hydrochloride Extended-Release Capsules in Premarketing Clinical Studies

Indication	Venlafaxine Hydrochloride Extended-Release Capsules
MDD	705 a
GAD	1,381
SAD	819
PD	1,314

^a In addition, in the premarketing assessment of venlafaxine hydrochloride, multiple doses were administered to 2,897 patients in studies for MDD.
The incidences of common adverse reactions (those that occurred in ≥ 2% of venlafaxine hydrochloride extended-release capsules treated patients [357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients] and more frequently than placebo) in venlafaxine hydrochloride extended-release capsules treated patients in short-term, placebo-controlled, fixed-and flexible-dose clinical studies (doses 37.5 to 225 mg per day) are shown in Table 9.
The adverse reaction profile did not differ substantially between the different patient populations. Table 9: Common Adverse Reactions: Percentage of Patients Reporting Adverse Reactions (≥ 2% and > placebo) in Placebo-controlled Studies (up to 12 Weeks Duration) across All Indications

Body System Adverse Reaction	Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558	Placebo n = 2,197
Body as a whole
Asthenia	12.6	7.8
Cardiovascular system
Hypertension	3.4	2.6
Palpitation	2.2	2
Vasodilatation	3.7	1.9
Digestive system
Anorexia	9.8	2.6
Constipation	9.3	3.4
Diarrhea	7.7	7.2
Dry mouth	14.8	5.3
Nausea	30	11.8
Vomiting	4.3	2.7
Nervous system
Abnormal dreams	2.9	1.4
Dizziness	15.8	9.5
Insomnia	17.8	9.5
Libido decreased	5.1	1.6
Nervousness	7.1	5
Paresthesia	2.4	1.4
Somnolence	15.3	7.5
Tremor	4.7	1.6
Respiratory system
Yawn	3.7	0.2
Skin and appendages
Sweating (including night sweats)	11.4	2.9
Special senses
Abnormal vision	4.2	1.6
Urogenital system
Abnormal ejaculation/orgasm (men) a	9.9	0.5
Anorgasmia (men) a	3.6	0.1
Anorgasmia (women) b	2	0.2
Impotence (men) a	5.3	1

^a Percentages based on the number of men (venlafaxine hydrochloride extended-release capsules, n = 1,440; placebo, n = 923)
^b Percentages based on the number of women (venlafaxine hydrochloride extended-release capsules, n = 2,118; placebo, n = 1,274)
Other Adverse Reactions Observed in Clinical Studies
Body as a whole – Photosensitivity reaction, chills
Cardiovascular system – Postural hypotension, syncope, hypotension, tachycardia
Digestive system – Gastrointestinal hemorrhage [see Warnings and Precautions ( 5.4)], bruxism
Hemic/Lymphatic system – Ecchymosis [see Warnings and Precautions ( 5.4)]
Metabolic/Nutritional – Hypercholesterolemia, weight gain [see Warnings and Precautions ( 5.10)], weight loss [see Warnings and Precautions ( 5.10)]
Nervous system – Seizures [see Warnings and Precautions ( 5.8)], manic reaction [see Warnings and Precautions ( 5.6)], agitation, confusion, akathisia, hallucinations, hypertonia, myoclonus, depersonalization, apathy
Skin and appendages – Urticaria, pruritus, rash, alopecia
Special senses – Mydriasis, abnormality of accommodation, tinnitus, taste perversion Urogenital system – Urinary retention, urination impaired, urinary incontinence, urinary frequency increased, menstrual disorders associated with increased bleeding or increased irregular bleeding (e.g., menorrhagia, metrorrhagia)