Venlafaxine formulation

Maprotiline, Moclobemide, Mianserin, Fluoxetine (Prozac), Paroxetine, Sertraline, Fluvoxamine, Citalopram, Venlafaxin (generic IR formulation and the brand Venlafaxine XR), Mirtazapine, Flupentixol-melitracen (Deanxit), Tianeptine, Extract of St. John s Wort, Buspirone Depression and anxiety... 

E. Nefazodone,fluoxetine,mirtazapine, and venlafaxine have minimal effects on seizure threshold. Bupropion in its original formulation caused seizures in 4 in 1000 patients. Although this has been reduced with the slow release form of the medication (Wellbutrin SR), it remains a contraindication to prescribe this medication to patients with a history of seizures. 

Optimal dosing with venlafaxine differs from that of both TCAs and SSRIs. Venlafaxine is like the SSRIs and different from the TCAs in that a therapeutic dose (i.e., 75 mg per day) can be started from the beginning. Unlike the SSRIs, however, dose escalation with venlafaxine does increase the magnitude of the antidepressant effect, which supports increasing the dose in the event of an inadequate response to the initial trial ( Table 7-9). Venlafaxine in its sustained release formulation can be given once a day, just like the SSRIs and TCAs. 

Unlike venlafaxine and the SSRIs, nefazodone in adults is started at 200 mg per day and then requires at least a one time increase to 300 mg per day to achieve an effective dose. Similar to the immediate release formulation of venlafaxine, nefazodone requires twice-a-day administration and may induce a greater response rate with higher doses if the patient fails to respond initially. Thus, like venlafaxine, nefazodone appears to have a dual mechanism of action, although the specific mechanisms involved are different for these two agents. At lower doses, the most potent action of nefazodone is 5-HT 2 blockade, whereas higher concentrations produce greater inhibition of the 5-HT uptake pump ( 254, 255 and 256). 

The biotransformation of venlafaxine to its active metabolite, ODV, is dependent on CYP 2D6 (138, 306). The further elimination of ODV is dependent on CYP 3A3/4. Venlafaxine and ODV have approximate half-lives of 5 and 11 hours, respectively. Because venlafaxine and ODV have virtually identical pharmacological profiles, both are believed to contribute equally to the patient s overall response in terms of both efficacy and adverse effects ( 141). The 11-hour half-life of ODV is consistent with the fact that the immediate release formulation of venlafaxine is efficacious when administered twice daily. 

Initially, plasma and oral fluid specimens from patients (n = 21) on different antidepressant treatment were collected twice to assess if any of the studied analytes was likely to show a good correlation. The best results were obtained for venlafaxine (%CV for plasma/oral fluid concentrations ratio (f OF/PL) <21%). Therefore, the study was extended for this antidepressant by analysis of oral fluid and plasma specimens from five patients on venlafaxine treatment collected on four occasions. Daily doses of venlafaxine retard formulations were 75 mg for two patients, and 150 mg for the remaining participants. Collection of oral fluid (direct spitting into polypropylene tubes) and plasma (heparinized tubes) specimens was performed, when possible, before the next dose to ensure the drug was in the elimination phase. The dose and the time of collection was the same on the four different occasions for each patient. For the analysis, oral fluid and plasma specimens were centrifuged at 14 x 103 rpm, and 0.2 mL of the supernatant were extracted. In addition, correlation between the concentrations in the plasmatic free fraction and in oral fluid was also evaluated. Plasmatic proteins were eliminated by filtering 0.5 mL of plasma samples using Microcon filter devices Ultracel YM-3 (Millipore Corp., Billerica, MA, USA). 

Drugs that potentiate serotonin function can cause ejaculatory delay in men, and this has led to the use of SSRIs to treat premature ejaculation (SEDA-26, 13). Venlafaxine is also reported to cause problems with ejaculation during routine use and its efficacy has been studied in a placebo-controlled, crossover study in 31 men with ejaculation latencies of less than 2 minutes (25). Both placebo and venlafaxine (75 mg/day of the XL formulation) significantly increased latency to ejaculation over baseline, placebo by 2 minutes and venlafaxine by 3 minutes there was no difference between the two treatments. The authors concluded that venlafaxine is not effective for the management of premature ejaculation. However, the small number of subjects studied and the large placebo effect makes this conclusion tentative. It does appear, however, that the effect of venlafaxine on ejaculation delay is probably less striking than, for example, that of paroxetine. 

In this section, practical examples demonstrating the formulation and process development of extended-release matrices are presented. Verapamil hydrochloride (HCl) (soluble), metformin HCl (freely soluble), carbamazepine (practically insoluble) and venlafaxine HCl (freely soluble) extended-release matrix formulations are used to illustrate the different formulation and manufacturing principles (direct compression and wet granulation). 

The last example is of conformational polymorphs and multiple Z in an active pharmaceutical ingredient, commonly referred to as API. Venlafaxine 10 is a serotonin-norepinephrine reuptake inhibitor dmg (SNRI) for treating anxiety and depression, and marketed as the hydrochloride salt formulation in forms 1 and/or 2. 

Sherman, D.M. Extended release formulation containing Venlafaxine, EP 797991 Bl, 1997, 9pp. 

A.R. Madgulkar, M.R. Bhalekar, V.J. Kolhe, Y.D. Kenjale, Formulation and optimization of sustained release tablets of venlafaxine resinates using response surface methodology, Indian J Pharm Sci, 71 (4), 387, 2009... 

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