Metamizole (Novalgin®)

Metamizole (the active ingredient in Novalgin®) is a highly effective pain reliever from the pyrazolone group. It relieves pain, reduces fever and additionally has an antispasmodic (spasmolytic) effect on smooth muscle.

In Germany, metamizole is prescription-only; in many other countries it has even been withdrawn from the market – due to the rare but serious risk of agranulocytosis (a severe drop in white blood cells).

Despite this risk, metamizole is widely used in Germany and is valued as a strong analgesic, particularly for colic and postoperative pain. The drop formulation (Novalgin® drops) allows flexible dosing.

The mechanism of action of metamizole is not fully understood:

Suspected mechanisms:

• Inhibition of cyclooxygenase (COX) in the central nervous system
• Activation of the descending pain-inhibiting system
• Inhibition of prostaglandin E2 synthesis
• Direct spasmolytic effect on smooth muscle

Effect profile:

• Strongly analgesic
• Strongly antipyretic: Very effective against high fever
• Spasmolytic: Relieves spasms of smooth muscle (colic)
• Not anti-inflammatory: No clinically relevant anti-inflammatory effect

Pharmacokinetics:

• Onset of action: 30–60 minutes (oral)
• Duration of action: 4–6 hours

Metamizole is suitable for:

• Severe pain when other medications are not sufficient
• Colic pain (gallbladder, kidney, bowel)
• Postoperative pain
• Tumor pain
• High fever that does not respond to other measures

Advantages:

• No respiratory depression (unlike opioids)
• Antispasmodic effect in colic

Not suitable:

• In bone marrow disorders
• In genetic glucose-6-phosphate dehydrogenase deficiency
• In acute hepatic porphyria
• In the 3rd trimester of pregnancy (generally not recommended in the 1st and 2nd trimesters)

Drops (Novalgin® drops):

• 500 mg/ml (20 drops = approx. 500 mg)

Tablets:

• 500 mg

Usual dosage (adults):

• 500–1000 mg as a single dose
• Up to 4 times daily
• Maximum daily dose: 4000 mg (4 g)

Drop dosage:

• 20–40 drops as a single dose
• Corresponds to 500–1000 mg

Drops:

• Take in a little water or on a sugar cube
• Count out the exact number of drops

Tablets:

• Take with sufficient water
• With or without food

Important notes:

• Do not take long term without medical supervision
• If you develop fever or a sore throat during treatment, see a doctor immediately (agranulocytosis!)
• Regular blood count checks during long-term use
• May turn the urine reddish (harmless)

Metamizole must not be taken in case of:

• Hypersensitivity to pyrazolones
• Disorders of bone marrow function
• Genetic glucose-6-phosphate dehydrogenase deficiency
• Acute hepatic porphyria
• In the 3rd trimester of pregnancy

Caution in case of:

• Pregnancy in the 1st and 2nd trimesters (use generally not recommended)
• Breastfeeding (avoid repeated use, after a single use collect and discard breast milk for 48 hours)
• Bronchial asthma or chronic urticaria
• Hypotension (drop in blood pressure possible)
• Renal or hepatic insufficiency
• Concomitant use of cyclosporine

Uncommon:

• Skin rash, urticaria
• Drop in blood pressure (dose-dependent)

Rare but serious:

• Agranulocytosis: Severe drop in white blood cells
• Frequency: approx. 1:1 million per use
• Symptoms: fever, sore throat, mucosal ulcers
• See a doctor immediately and have your blood count checked!
• Can be fatal
• Anaphylactic reactions
• Severe skin reactions (Stevens-Johnson syndrome)
• Drug-induced liver injury with acute hepatitis, jaundice or elevated liver enzymes (frequency not known)
• In isolated cases progressing to acute liver failure
• If there are signs of liver damage, see a doctor

Note: Agranulocytosis is not dose-dependent and can occur even after a single dose. It is the reason for the restrictive handling in many countries.

Relevant interactions:

• Cyclosporine, tacrolimus, bupropion, efavirenz, methadone, valproate, sertraline – levels and effectiveness may decrease
• Low-dose acetylsalicylic acid for heart protection (effect on platelets may be reduced)
• Methotrexate – increased toxicity possible
• Chlorpromazine – increased hypothermia

Interactions known for pyrazolones (whether they also occur with metamizole is not known):

• Oral anticoagulants, captopril, lithium, triamterene
• Antihypertensives and diuretics (effectiveness may change)

Combination possible with:

• Paracetamol (additive effect)
• NSAIDs (different mechanisms of action)
• Weak opioids