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Metamizole — known under the trade names Novalgin®, Novaminsulfon, Berlosin and Analgin — is one of the most commonly prescribed pain relievers in Germany. It has a strong pain-relieving, antipyretic and antispasmodic effect and is used almost routinely in clinics.At the same time, metamizole is banned or withdrawn from the market in many countries — including the USA, Great Britain, France and Sweden. The reason: rare but potentially fatal agranulocytosis. In December 2024, the BfArM issued a new red-hand letter that intensifies the warning signs. This guide explains what you need to know.
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Metamizole only for an approved indication and under medical supervision. For fever, a sore throat, or mucosal changes on metamizole: stop immediately and see a doctor. This article does not replace medical advice.
Metamizole (active substance name: metamizole sodium, trade name: Novalgin®) is one of the strongest non-opioid painkillers – and at the same time one of the most controversial. In Germany it is prescription-only and widely used. In the USA, the United Kingdom, and large parts of northern Europe it has been banned for decades. The reason: the risk of a rare but life-threatening side effect – agranulocytosis.
| Property | Details |
|---|---|
| Active substance | Metamizole sodium (= novaminsulfone) |
| ATC code | N02BB02 |
| Substance class | Pyrazolones (non-opioid analgesic) |
| Trade names | Novalgin®, Novaminsulfon, Berlosin, Analgin |
| Available forms | Film-coated tablets 500 mg, drops 500 mg/ml, injection solution, suppositories |
| Half-life | 2–4 hours (active metabolites longer) |
| Maximum dose | 4,000 mg/day (4 × 500–1,000 mg) |
| Prescription status | Yes (in Germany) |
| Special feature | Banned in the USA, UK, France, Sweden, Norway, Denmark |
Anyone who brings the familiar Novalgin drops back from a holiday in Spain or Portugal may be surprised: there, metamizole is in part available without a prescription. Anyone who asks a British or American doctor for metamizole meets incomprehension: in these countries it has been withdrawn from the market for decades. How can the same medicine be routinely prescribed in one country and completely banned in another?
| Country / region | Status | Reason |
|---|---|---|
| Germany, Austria, Switzerland | Prescription-only | Available under a strict indication |
| Spain, Portugal, Italy, Poland | Approved (partly OTC!) | Broad availability |
| USA | Banned (since 1977) | Agranulocytosis risk |
| United Kingdom | Banned | Agranulocytosis risk |
| France | Banned | Agranulocytosis risk |
| Sweden, Norway, Denmark | Banned / off the market | Agranulocytosis risk |
| Finland | Market withdrawal 2024 | EMA review |
The answer lies in a different risk-benefit assessment. The countries that have banned metamizole judged the agranulocytosis risk as too high for broad use. Germany and other countries come to a different conclusion: under a strict indication – that is, only for severe pain that other agents cannot adequately control – metamizole is indispensable. Especially for colic (biliary, renal colic) it has a unique spasmolytic effect that no other painkiller can replace. And for patients in whom NSAIDs are contraindicated because of heart disease, stomach ulcers, or kidney problems, metamizole fills a therapeutic gap. With the Dear Doctor safety letter of 2024, the EMA further specified the framework for its use.
The exact mechanism of action of metamizole is to this day not fully clarified – which makes it pharmacologically unique. It is converted in the body into active metabolites (mainly 4-methylaminoantipyrine), which probably act via several pathways at the same time: by inhibiting prostaglandin synthesis (similar to NSAIDs, but with a different profile), by a direct spasmolytic effect on smooth muscle (particularly relevant in colic), and by central pain inhibition via the endogenous cannabinoid system as well as descending pain-inhibiting pathways in the spinal cord.
This combined mechanism of action explains why metamizole is particularly effective for certain types of pain: for visceral pain (colic), postoperative pain, and tumour pain – situations in which classic NSAIDs or paracetamol are often not enough.
This is decisive both pharmacologically and legally: metamizole is not an everyday painkiller and not a replacement for ibuprofen or paracetamol for mild to moderate pain. It may only be used when other measures are not enough or are contraindicated. This principle is frequently violated in practice.
| Approved indications | Not approved (frequent off-label misuse) |
|---|---|
| Acute severe pain after surgery / injury | Mild to moderate headaches |
| Colic (biliary, renal colic) | Everyday pain (back, joints) |
| Tumour pain | Toothache (1st choice = ibuprofen!) |
| High fever (when other measures fail) | Fever without exhausting other options |
| Chronic severe pain (when alternatives fail) | Routine long-term therapy |
| Age group | Single dose | Max. daily dose | Note |
|---|---|---|---|
| Adults | 500–1,000 mg | 4,000 mg (4×1,000 mg) | Dosing interval ≥ 6 hours |
| Children (> 3 months) | Weight-adapted | Weight-adapted | Drops preferred (exact dosing) |
| Older patients | Start low | Individual adjustment | Hypotension risk increased! |
| Kidney impairment | Reduced | Individual | Active metabolites accumulate |
| Liver impairment | Reduced | Individual | Hepatic metabolism |
Agranulocytosis is the keyword that every metamizole patient must know. It describes a sudden, dramatic drop in the neutrophil granulocytes – the white blood cells that are responsible for defence against bacterial infections. When these cells fall below 500 per microlitre, the body's own infection defence is practically switched off. Even harmless bacteria can then lead to life-threatening sepsis.
What makes agranulocytosis so dangerous is its unpredictability. It is not dose-dependent – it can occur with the first tablet just as well as after weeks of trouble-free intake. There is no lab early-warning value, no risk group that one could identify. The mechanism is immunological: for reasons still unknown, the patient's immune system forms antibodies against metamizole metabolites on the surface of the granulocytes and destroys them.
| Fact | Detail |
|---|---|
| Frequency | Very rare (<1:10,000). With 1 week of treatment: about 1.1 per 1 million |
| Dose-dependent? | NO! Can occur at any dose and any duration of use |
| Timing | At any time – even after days or weeks. Median time: 6–15 days |
| Repeat risk | Considerably increased on renewed administration (sensitisation!) |
| Mechanism | Immunological (not toxic) – therefore dose-independent and unpredictable |
| Case fatality | 5–10% (when recognised and treated!) |
This is the most dangerous property of the agranulocytosis risk: metamizole is frequently used as a fever reducer. Agranulocytosis causes severe infections that manifest – like any infection – with fever. When a patient takes metamizole against fever and develops an agranulocytosis in the process, the metamizole lowers the fever that the agranulocytosis causes. The warning signal is suppressed. The diagnosis is delayed. The chance of timely treatment dwindles.
That is the reason why the BfArM warns particularly against using metamizole routinely as a fever reducer when paracetamol or ibuprofen are possible.
The Dear Doctor safety letter of 9 December 2024 – issued by the BfArM and EMA after a comprehensive European re-evaluation – has changed the practice of metamizole therapy in one important point.
The surprising core statement: routine blood count checks are no longer recommended. That sounds counterintuitive at first – shouldn't a medicine with a known risk of blood count changes be monitored particularly closely? But the data shows: agranulocytosis occurs so suddenly that even weekly blood draws do not allow reliable early detection. Days can lie between a normal blood count on Monday and a manifest agranulocytosis on Wednesday. Blood checks give a false sense of security.
Instead, the 2024 Dear Doctor safety letter relies on consistent patient education: every patient must know the warning signs of an agranulocytosis and know what to do immediately if they occur. That is the only reliable protection – not a lab, but informed patients.
Particularly important: these warning signs also apply after stopping. The agranulocytosis can still manifest days after the last metamizole tablet. So anyone who has taken metamizole and then develops fever with a sore throat must act immediately – even if they have already stopped the medicine.
