Metamizole sodium × Venlafaxine

No label names this pair. The risks come from the properties of each drug. Metamizole can cause agranulocytosis, and this reaction does not depend on the dose (metamizole label). The venlafaxine label also lists agranulocytosis, neutropenia and aplastic anaemia among rare adverse reactions, and thrombocytopenia among very rare ones. Venlafaxine may reduce platelet function and raises the risk of bleeding, including gastrointestinal bleeding (venlafaxine label). Gastrointestinal bleeding has also occurred with metamizole. Many of those patients were taking other drugs linked to such bleeding, such as nonsteroidal anti-inflammatory drugs (metamizole label). Metamizole may act partly through the central nervous system (metamizole label), and the venlafaxine labels ask for caution with other drugs active in the central nervous system. Metamizole induces the enzymes CYP2B6 and CYP3A4 and may lower the levels of the drugs its label names, but venlafaxine is not on that list. The enzyme CYP2D6 mainly converts venlafaxine to its active metabolite (both labels).

Bleeding with venlafaxine ranges from bruises, haematomas, nosebleeds and petechiae to life-threatening gastrointestinal bleeding (venlafaxine label). Gastrointestinal bleeding shows as black stools, vomiting blood or coffee-ground material, and weakness. Agranulocytosis starts with fever, chills, sore throat and painful changes in the lining of the mouth, nose, throat, genital or anal area. Metamizole lowers fever, so some of these signs may go unnoticed (metamizole label). Other signs of a blood disorder are bruising, bleeding, pallor, persistent fever and general malaise (metamizole label).

The combination is acceptable under supervision. No label forbids it or names the pair. The venlafaxine labels advise caution when it is taken with other substances active in the central nervous system (Spanish Agency of Medicines and Medical Devices, AEMPS, section 4.5; US Food and Drug Administration, FDA, section 7.2). Use venlafaxine with caution in patients predisposed to bleeding (AEMPS, 4.4). Tell the patient to stop metamizole and contact a doctor straight away if fever, sore throat, mouth ulcers, bruising, bleeding or pallor appear (metamizole label, 4.4). If agranulocytosis is suspected, order a full blood count with differential and stop metamizole without waiting for the result. If agranulocytosis is confirmed, do not restart metamizole (metamizole label, 4.4). In older patients and in renal or hepatic impairment, give metamizole only after weighing benefit against risk (metamizole label, 4.4). Venlafaxine is not on the list of drugs whose levels metamizole lowers through enzyme induction, and the labels give no other guidance on the kinetics of this pair (metamizole label, 4.5).