Venlafaxine Hydrochloride (Page 6 of 13)

Adverse Findings Observed in Short-Term, Placebo-Controlled Studies with Venlafaxine Hydrochloride Extended-Release Capsules

Adverse Reactions Associated with Discontinuation of Treatment

Major Depressive Disorder: Approximately 11% of the 357 patients who received venlafaxine hydrochloride extended-release capsules in placebo-controlled clinical trials for major depressive disorder discontinued treatment due to an adverse reaction, compared with 6% of the 285 placebo-treated patients in those studies. Adverse reactions that led to treatment discontinuation in a least 2% of drug-treated patients were nausea, dizziness, and somnolence.

Social Anxiety Disorder: Approximately 17% of the 277 patients who received venlafaxine hydrochloride extended-release capsules in placebo-controlled clinical trials for Social Anxiety Disorder discontinued treatment due to an adverse reaction, compared with 5% of the 274 placebo-treated patients in those studies. Adverse reactions that led to treatment discontinuation in a least 2% of drug-treated patients were nausea, insomnia, impotence, headache, dizziness, and somnolence.

Adverse Reactions Occurring at an Incidence of 5% or More

Major Depressive Disorder: Note in particular the following adverse reactions that occurred in at least 5% of the patients receiving venlafaxine hydrochloride extended-release capsules and at a rate at least twice that of the placebo group for all placebo-controlled trials for the major depressive disorder indication (see Table 6): Abnormal ejaculation, gastrointestinal complaints (nausea, dry mouth, and anorexia), CNS complaints (dizziness, somnolence, and abnormal dreams), and sweating. In the two U.S. placebo-controlled trials, the following additional reactions occurred in at least 5% of patients treated with venlafaxine hydrochloride extended-release capsules (n = 192) and at a rate at least twice that of the placebo group: Abnormalities of sexual function (impotence in men, anorgasmia in women, and libido decreased), gastrointestinal complaints (constipation and flatulence), CNS complaints (insomnia, nervousness, and tremor), problems of special senses (abnormal vision), cardiovascular effects (hypertension and vasodilatation), and yawning.

Social Anxiety Disorder: Note in particular the following adverse reactions that occurred in at least 5% of the patients receiving venlafaxine hydrochloride extended-release capsules and at a rate at least twice that of the placebo group for the 2 placebo-controlled trials for the Social Anxiety Disorder indication (see Table 7): Asthenia, gastrointestinal complaints (anorexia, constipation, dry mouth, nausea), CNS complaints (dizziness, insomnia, libido decreased, nervousness, somnolence), abnormalities of sexual function (abnormal ejaculation, impotence, libido decreased, orgasmic dysfunction), yawn, sweating, and abnormal vision.

Adverse Reactions Occurring at an Incidence of 2% or More Among Patients Treated with Venlafaxine Hydrochloride Extended-Release Capsules

Tables 6 and 7 enumerate the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of major depressive disorder (up to 12 weeks; dose range of 75 to 225 mg/day) and of Social Anxiety Disorder (up to 12 weeks; dose range of 75 to 225 mg/day), respectively, in 2% or more of patients treated with venlafaxine hydrochloride extended-release capsules where the incidence in patients treated with venlafaxine hydrochloride extended-release capsules was greater than the incidence for the respective placebo-treated patients. The table shows the percentage of patients in each group who had at least one episode of a reaction at some time during their treatment. Reported adverse reactions were classified using a standard COSTART-based Dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of adverse reactions in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reaction incidence rate in the population studied.

Table 6 Treatment-Emergent Adverse Reaction Incidence in Short-Term Placebo-Controlled Clinical Trials with Venlafaxine Hydrochloride Extended-Release Capsules in Patients with Major Depressive Disorder *^, †

	% Reporting Reaction
Body System Preferred Term	Venlafaxine Hydrochloride Extended-Release Capsules	Placebo
	(n = 357)	(n = 285)
* Incidence, rounded to the nearest %, for reactions reported by at least 2% of patients treated with venlafaxine hydrochloride extended-release capsules, except for reactions which had an incidence equal to or less than placebo. † <1% indicates an incidence greater than zero but less than 1%. ‡ Mostly “hot flashes.” § Mostly “vivid dreams,” “nightmares,” and “increased dreaming.” ¶ Mostly “blurred vision” and “difficulty focusing eyes.” # Mostly “delayed ejaculation.” Þ Incidence is based on the number of male patients. ß Mostly “delayed orgasm” or “anorgasmia.” à Incidence is based on the number of female patients.
Body as a Whole
Asthenia	8%	7%
Cardiovascular System
Vasodilatation ‡	4%	2%
Hypertension	4%	1%
Digestive System
Nausea	31%	12%
Constipation	8%	5%
Anorexia	8%	4%
Vomiting	4%	2%
Flatulence	4%	3%
Metabolic/Nutritional
Weight Loss	3%	0%
Nervous System
Dizziness	20%	9%
Somnolence	17%	8%
Insomnia	17%	11%
Dry Mouth	12%	6%
Nervousness	10%	5%
Abnormal Dreams §	7%	2%
Tremor	5%	2%
Depression	3%	<1%
Paresthesia	3%	1%
Libido Decreased	3%	<1%
Agitation	3%	1%
Respiratory System
Pharyngitis	7%	6%
Yawn	3%	0%
Skin
Sweating	14%	3%
Special Senses
Abnormal Vision ¶	4%	<1%
Urogenital System
Abnormal Ejaculation (male)#, Þ	16%	<1%
Impotence Þ	4%	<1%
Anorgasmia (female)ß, à	3%	<1%

Table 7 Treatment-Emergent Adverse Reaction Incidence in Short-Term Placebo-Controlled Clinical Trials with Venlafaxine Hydrochloride Extended-Release Capsules in Social Anxiety Disorder Patients *^, †

	% Reporting Reaction
Body System Preferred Term	Venlafaxine Hydrochloride Extended-Release Capsules	Placebo
	(n =277)	(n = 274)
* Adverse reactions for which the venlafaxine hydrochloride extended-release capsules reporting rate was less than or equal to the placebo rate are not included. † <1% means greater than zero but less than 1%. ‡ Mostly “hot flashes.” § Mostly “decreased appetite” and “loss of appetite.” ¶ Mostly “vivid dreams,” “nightmares,” and “increased dreaming.” # Mostly “blurred vision.” Þ Includes “delayed ejaculation” and “anorgasmia.” ß Percentage based on the number of males (venlafaxine hydrochloride extended-release capsules = 158, placebo = 153). à Includes “abnormal orgasm” and “anorgasmia.” è Percentage based on the number of females (venlafaxine hydrochloride extended-release capsules = 119, placebo = 121).
Body as a Whole
Headache	34%	33%
Asthenia	17%	8%
Flu Syndrome	6%	5%
Accidental Injury	5%	3%
Abdominal Pain	4%	3%
Cardiovascular System
Hypertension	5%	4%
Vasodilatation ‡	3%	1%
Palpitation	3%	1%
Digestive System
Nausea	29%	9%
Anorexia §	20%	1%
Constipation	8%	4%
Diarrhea	6%	5%
Vomiting	3%	2%
Eructation	2%	0%
Metabolic/Nutritional
Weight Loss	4%	0%
Nervous System
Insomnia	23%	7%
Dry Mouth	17%	4%
Dizziness	16%	8%
Somnolence	16%	8%
Nervousness	11%	3%
Libido Decreased	9%	<1%
Anxiety	5%	3%
Agitation	4%	1%
Tremor	4%	<1%
Abnormal Dreams ¶	4%	<1%
Paresthesia	3%	<1%
Twitching	2%	0%
Respiratory System
Yawn	5%	<1%
Sinusitis	2%	1%
Skin
Sweating	13%	2%
Special Senses
Abnormal Vision #	6%	3%
Urogenital System
Abnormal Ejaculation Þ, ß	16%	1%
Impotence ß	10%	1%
Orgasmic Dysfunction à, è	8%	0%