Panobinostat and Paxil CR

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using panobinostat together with PARoxetine may increase the risk of bleeding. Panobinostat may also increase the blood levels and effects of PARoxetine. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. Contact your doctor if your condition changes or you experience increased side effects, such as palpitations, fainting, chest pain, muscle stiffness or weakness, shaking, or tremors. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness, lightheadedness, red or black tarry stools, coughing up or vomiting fresh or dried blood that looks like coffee grounds, severe headache, and weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR CLOSELY: Coadministration of panobinostat and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications, including selective serotonin reuptake inhibitors (SSRIs) and other agents with serotonin reuptake inhibitor (SRI) properties, such as clomipramine. Treatment with panobinostat has been associated with severe thrombocytopenia and hemorrhage (including gastrointestinal and pulmonary hemorrhage) with fatal outcomes. This risk may be increased in patients with coagulation disorders or those on chronic anticoagulation therapy. In a phase III clinical trial in patients with relapsed multiple myeloma, treatment-emergent grade 3 to 4 (CTCAE) thrombocytopenia and hemorrhage was reported in 67% and 4.2% of panobinostat-treated patients, respectively. In the same clinical trial, there were 5 patients treated with panobinostat who died due to a hemorrhagic event, compared to one in the control arm. The patients with fatal bleeding events had at least grade 3 (CTCAE) thrombocytopenia at the time of the event. In addition, serotonin release by platelets plays an important role in hemostasis, thus SSRIs may alter platelet function and induce bleeding. Bleeding events related to SSRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Epidemiological studies have confirmed the association between the use of these agents and the occurrence of upper gastrointestinal bleeding, and concurrent use of NSAIDs or aspirin was found to potentiate the risk. Concomitant administration of paroxetine and warfarin has been associated with an increased frequency of bleeding without apparent changes in the disposition of either drug or changes in the prothrombin time. Bleeding has also been reported with fluoxetine and warfarin, while citalopram and sertraline have been reported to prolong the prothrombin time of patients taking warfarin by about 5% to 8%. In the RE-LY study (randomized evaluation of long-term anticoagulant therapy), SSRIs were associated with an increased risk of bleeding in all treatment groups. In addition, coadministration with panobinostat may increase the plasma concentrations of drugs that are substrates of CYP450 2D6, including but not limited to SSRIs such as duloxetine, fluoxetine, fluvoxamine, paroxetine, and venlafaxine, as well as clomipramine, which has strong SRI properties. When a single 60 mg dose of dextromethorphan, a CYP450 2D6 probe substrate, was coadministered with panobinostat (20 mg once per day on days 3, 5, and 8) in 14 patients with advanced cancer, dextromethorphan peak plasma concentration (Cmax) increased by 20% to 200% (median 80%) and systemic exposure (AUC) increased by 20% to 130% (median 60%) compared to administration of dextromethorphan alone.

MANAGEMENT: Caution is recommended when panobinostat is used in combination with SSRIs or other medicines with SRI properties. Close clinical and laboratory observation for bleeding complications is recommended during therapy. A complete blood cell count should be performed prior to and at least weekly during treatment per treatment protocols, including monitoring for thrombocytopenia. Dose modifications may be required based on individual patient tolerability. Monitoring for side effects associated with increased levels of SSRIs such as confusion, tachycardia, tremor, or nausea, should also be considered. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools. Since panobinostat is indicated in combination with bortezomib and dexamethasone, the manufacturer labeling for these products should also be consulted for additional information.

Panobinostat

Generic Name: panobinostat

Brand name: Farydak

Synonyms: n.a.

What is Panobinostat?

Paxil CR

Generic Name: paroxetine

Brand name: Brisdelle, Paxil, Paxil CR, Pexeva

Synonyms: n.a.

What is Paxil CR?