Venlafaxine administration

Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R (1997) Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 58 348-350... 

Serotonin re-uptake inhibitors are readily absorbed after oral administration and widely distributed throughout the body. Elimination is mainly by hepatic metabolism. Fluoxetine, sertraline and venlafaxine are demethylated to active metabolites. 

Venlafaxine is rapidly absorbed following oral administration. Venlafaxine = 5 hours) is metabolized through the CYP450-2D6 and CYP450-3A4 systems to its active metabolite, O-desmethylvenlafaxine = 11 hours), and is excreted through the kidney (Kla-merus et al., 1992). 

Venlafaxine is approved by the U.S. Food and Drug Administration for the treatment of both major depression and generalized anxiety disorder. Preliminary data suggest that it might also have a role in the treatment of chronic pain conditions and perhaps other disorders against which SSRIs are effective. Serotonin reuptake inhibition is prominent at lower doses of venlafaxine at higher doses, inhibition of norepinephrine reuptake becomes more significant. 

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). 

Venlafaxine presentation to the Food and Drug Administration Psychopharmacology Advisory Committee. Washington, DC, April 1993. 

Administration of the CYP2D6 inhibitor quinidine, 200 mg/day for 2 days, to the extensive metabolizers reduced the oral clearance of venlafaxine to the level seen in poor metabolizers. Quinidine had no effect on venlafaxine clearance in subjects who were poor metabolizers before treatment. The authors suggested that poor metabolizers may be at particular risk of venlafaxine toxicity, as could subjects who take inhibitors of CYP2D6. 

Kilic S, Ergin H, Baydinc YC. Venlafaxine extended release for the treatment of patients with premature ejaculation a pilot, single-blind, placebo-controlled, fixed dose crossover study on short-term administration of an antidepressant drug. Int J Androl 2005 28 47-52. 

Estrogen is more effective than any other therapy in relieving vasomotor symptoms, and aU types and routes of systemic administration are equally effective in a dose-dependent fashion. If treatment can be tapered and stopped within 5 years, no evidence of increased risk of breast cancer is seen. Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

ASPIRIN VENLAFAXINE Possible t risk of bleeding with venlafaxine Uncertain Avoid co-administration with high-dose aspirin... 

INDIRECT SSRIs 1. Case report of serotonin syndrome when dexamfetamine was co-administered with citalopram 2. Case reports of psychiatric disturbances when methylphenidate was given with sertraline and phenylpropanolamine co-adminis-tered with phenylpropanolamine 1. Uncertain postulated that it is an additive effect of the inhibition of serotonin reuptake by citalopram with the release of serotonin by venlafaxine 2. Uncertain 1. Avoid co-administration of dexamfetamine and citalopram 2. Warn patients to watch for early signs such as anxiety... 

INDIRECT OTHER-VENLAFAXINE Case report of serotonin syndrome when dexamfetamine was coadministered with venlafaxine Uncertain postulated to be an additive effect of the inhibition of serotonin reuptake by venlafaxine and the release of serotonin by venlafaxine Avoid co-administration... 

LITHIUM OTHER-VENLAFAXINE Possible risk of serotonin syndrome Additive effect Be aware of the possibility of serotonin syndrome. Also need to monitor lithium levels with appropriate dose adjustments during co-administration >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

FLUOXETINE, PAROXETINE, SERTRALINE, VENLAFAXINE ZOLPIDEM Cases of agitation hallucinations Uncertain Avoid co-administration... 

SNRIs ANTIMALARIALS - ARTEMETHER/ LUMEFANTRINE t artemether/lumefantrine levels with risk of toxicity, including arrhythmias Venlafaxine inhibits CYP3A4, which is partly responsible for the metabolism of artemether Avoid co-administration with venlafaxine and caution with duloxetine... 

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