Venlafaxine and Linezolid Injection: Interaction Details

a) In a retrospective cohort study (N=1134), serotonin syndrome occurred in fewer than 6 patients (less than 0.5%) who were taking a concurrent antidepressant and linezolid (n=215). In a propensity score-matched cohort (n=332), there was no significant difference in the risk of serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients not taking antidepressants (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). There was also no significant difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups. Clinically significant serotonin syndrome was defined as requiring an ambulatory care visit, emergency department visit, or hospitalization. Patients were 66 years of age or older, all were taking linezolid 600 mg orally twice daily, and of those taking antidepressants, 103 (47.9%) were taking an SSRI, 36 (16.7%) were taking an SNRI, 15 (7%) were taking a tricyclic antidepressant, 7 (3.3%) were taking a norepinephrine and dopamine reuptake inhibitor ¹.

b) A case report described serotonin toxicity in a 58-year-old woman following concomitant use of linezolid and venlafaxine. The patient, who had a history of urological problems after bladder resection for transitional cell carcinoma 18 years earlier and had undergone a bilateral total hip arthroplasty (THA), was being treated with venlafaxine 75 mg for severe depression and prior episodes of self-harm. She presented with symptoms of systemic infection. Increased activity at the site of the bilateral THA was revealed and a diagnosis of MRSA infection was made. Subsequently, the patient was initiated on vancomycin and rifAMPin intravenously. A 2-stage revision THA was performed due to the MRSA infection. Because of problems with intravenous antibiotic administration, her regimen was changed to oral linezolid and oral rifAMPin 2 weeks postoperatively. On day 4 following linezolid initiation, acute disorientation was observed. Physical examination and CT scan of the head did not reveal any abnormal findings or autonomic dysfunction. Over the next 24 hours, however, her condition deteriorated. Subsequently, linezolid and venlafaxine were stopped due to possible serotonin toxicity. The patient's condition normalized 48 hours after linezolid and venlafaxine were discontinued ³.

c) A case report described serotonin syndrome in a 36-year-old woman following the concomitant use of linezolid and venlafaxine. The patient, who had no history of seizures and whose regimen included lithium, venlafaxine, and imipramine for bipolar disorder, depression, and headaches, respectively, presented to the emergency room (ER) with seizures. Ten days prior to presenting to the ER, the patient received vancomycin for treatment of MRSA empyema. However, therapy was switched to linezolid approximately 36 hours before her ER visit. At presentation, she had a blood pressure (BP) of 234/196 mmHg, a heart rate of 160 beats/min, respiratory rate of 24 breaths/min, and diaphoresis. Her pupils were dilatated with slow reaction to light and she was unresponsive to verbal instructions. The patient was intubated and administered multiple doses of LORazepam, which lessened her tremors and decreased BP to 150/85 mmHg. Her serum lithium level was 1.2 mEq/L and there were no electrolyte abnormalities. Within 3 hours of intubation, mental status and breathing pattern normalized and the patient was extubated. While both imipramine and venlafaxine were withheld, lithium was continued and linezolid was replaced with trimethoprim and sulfamethoxazole. The patient remained alert and oriented over the following days and had reduced anxiety. Three weeks following discharge, the patient reported tremors and anxiety after reinstituting venlafaxine and imipramine. It was postulated that her 3 chronic serotonergic medications led to a baseline hyperserotonergic state, which was acutely aggravated by the addition of linezolid ⁴.

d) In one case report, a 30-year-old woman experienced symptoms of serotonin syndrome after concomitant treatment with linezolid and venlafaxine. After having received treatment since the age of 15 years for depression, social anxiety, bulimia, and alcohol/benzodiazepine abuse, she had become drug- and alcohol-free and was receiving extended-release venlafaxine 225 mg daily. After two weeks of treatment with linezolid, the patient complained of dizziness, syncope, and ataxia. At presentation, the patient appeared confused and disheveled. Venlafaxine was discontinued and intensive therapy was instituted. Although her neurological symptoms dissipated, she continued to experience rapid mood shifts, irritability, impulsivity, and insomnia for which quetiapine 25 mg 3 times daily was prescribed. Two weeks later, venlafaxine was gradually reinitiated ⁵.

e) A retrospective chart review identified one highly probable case of serotonin syndrome in a patient who received concomitant therapy with linezolid and venlafaxine, followed by citalopram. Charts of 72 inpatients who received linezolid and an SSRI or venlafaxine within 14 days of each other were reviewed for a diagnosis of serotonin syndrome (SS) using the Sternbach and the Hunter Serotonin Toxicity criteria. Of these patients, 52 (72%) were treated concomitantly with linezolid and an SSRI or venlafaxine. Four patients met the criteria for having either high or low probability of SS. Of these, one case involved an 81-year-old woman who was diagnosed with a high probability of having SS after receiving concomitant linezolid and venlafaxine followed by citalopram. Linezolid was given for a vancomycin-resistant Enterococcus urinary tract infection. When the patient presented, she refused to eat, was confused as to time and place, and began shouting. Although she appeared to have met 6 of the Sternbach criteria and 4 of the Hunter criteria for SS, a diagnosis of SS was not documented in her chart. Her blood pressure was 180 mm Hg with a heart rate of 120 beats/min, and a respiratory rate of 50 breaths/min. The following day, she barely spoke and could not be aroused; additional symptoms included lethargy, extremity twitching and jerking, eyes rolled back in her head, and labored breathing. Linezolid was discontinued, and she was sedated and intubated. Five days following onset of symptoms and 2 days after linezolid was stopped, she was extubated and had returned to baseline mental status with the ability to communicate ⁶.

f) A case report described serotonin toxicity in a 38-year-old woman following the concomitant administration of linezolid and venlafaxine. The patient, who had cystic fibrosis, fibromyalgia, and a recent rib fracture was admitted after 3 weeks of coughing, progressive dyspnea, and green-colored sputum. She had been receiving extended-release venlafaxine 300 mg once daily and gabapentin 100 mg 3 times daily for one year, and HYDROmorphone 1 mg every 4 hours as needed for the preceding 3 weeks. Due to a history of vancomycin intolerance, she was prescribed linezolid 600 mg IV every 12 hours for confirmed methicillin-resistant Staphylococcus aureus infection. Four days later, the patient had a blood pressure (BP) of 150/90 mmHg and experienced hot flashes, dyspnea, and tiredness. Eight days following linezolid initiation, the venlafaxine dose was reduced to 150 mg daily. The patient's hot flashes and headache persisted; additionally, she reported nervousness, muscle rigidity of the mouth, fine tremors (fingers), and involuntary arm, trunk, and leg movements. However, approximately 2 days after the venlafaxine dose reduction, her BP normalized to 142/84 mmHg; other symptoms dissipated the next day. Upon discharge on day 10, the patient was prescribed oral linezolid 600 mg twice daily for 4 days and venlafaxine 150 mg once daily. In the subsequent 2-year period, the patient received two 10-day courses of linezolid while receiving concomitant venlafaxine 187.5 mg and 225 mg daily with no symptoms of serotonin toxicity ⁷.

g) Serotonin syndrome was reported in the case of an 85-year-old man who was receiving venlafaxine 150 mg daily for depression and oral linezolid 600 mg twice daily with ciprofloxacin and rifAMPin for a closed wound due to the removal of a chronically infected hip prothesis. His medical history included Parkinson's disease, ischemic heart disease, atrial fibrillation, diabetes, and a permanent pacemaker. After 20 days of receiving oral antibiotic therapy, the patient was reportedly confused and disoriented with intermittent aggression and abnormal sleep patterns. A brain CT scan and serum chemistries were all normal with no evidence of sepsis; vital signs were also within normal limits. Four days later, the patient was transferred to an acute care rehabilitation hospital due to drowsiness. He had a fever of 37.6 degrees Celsius and a decreased level of consciousness, along with generalized myoclonic jerks and decreasing plantar reflexes. Linezolid and venlafaxine were discontinued due to a suspected drug interaction. Within 2 days, the patient's mental status had returned to normal ⁸.