Ibuprofen, ketoprofen, diclofenac and naproxen are among the best-selling medicines in Romanian pharmacies. They are effective and affordable, but frequently filed under "harmless" — which is false. Non-steroidal anti-inflammatory drugs (NSAIDs) have well-known gastrointestinal and cardiovascular side effects, documented in the ANMDMR SmPCs and in EMA recommendations. Here is how to choose them correctly.
How NSAIDs work
All NSAIDs inhibit the cyclooxygenase enzymes (COX-1 and COX-2), which produce prostaglandins — the molecules responsible for pain, fever and inflammation, but also for protecting the gastric mucosa and for renal function. Hence the paradox: the same inhibition that cuts your pain irritates your stomach. Selective COX-2 inhibitors (celecoxib, etoricoxib) protect the stomach better but raise cardiovascular risk.
Quick comparison of common NSAIDs
| Active substance | Usual adult dose | Half-life | Gastric risk | CV risk |
|---|---|---|---|---|
| Ibuprofen | 200-400 mg every 6-8h, max 1200 mg/day OTC | 2 h | Low-moderate | Low at OTC doses |
| Ketoprofen | 50-100 mg every 8-12h, max 200 mg/day | 2-3 h | Moderate | Moderate |
| Diclofenac | 50 mg every 8h, max 150 mg/day | 1-2 h | Moderate | Raised — EMA alert 2013 |
| Naproxen | 250-500 mg every 12h | 12-15 h | Moderate | Lowest among classic NSAIDs |
| Celecoxib | 100-200 mg/day | 11 h | Low | Moderate |
| Etoricoxib | 30-90 mg/day | 22 h | Low | Raised above 60 mg |
Source for the profiles: the summaries of product characteristics (SmPCs) published on anm.ro.
Concrete indications: what to choose for what
In Romanian pharmacy practice the questions sound the same: "What if I have a headache?", "For my back?", "For a child?". Here are some benchmarks:
- Tension headache, mild muscle pain: ibuprofen 200-400 mg or paracetamol 500-1000 mg. Paracetamol is gentler on the stomach; ibuprofen has the anti-inflammatory component.
- Dysmenorrhoea (period pain): ibuprofen 400 mg every 6-8 hours or ketoprofen — start at the first symptoms.
- Acute low back pain, muscle contracture: diclofenac (topical first — Voltaren Emulgel — and systemic only if topical is not enough), ketoprofen.
- Osteoarthritis with mechanical pain: paracetamol first line; NSAIDs only for short flare-up periods.
- Fever in a child >3 months: paracetamol first choice; paediatric ibuprofen (Nurofen for children) only above 6 months and 5 kg, watch for dehydration.
Gastric risks: what you need to know
NSAIDs are the main drug-related cause of gastric and duodenal ulcer. The risk rises in patients over 65, with a history of ulcer, when combined with corticosteroids, anticoagulants or another NSAID, and at high doses over a long period.
The guidelines (BNF, NICE, EMA) recommend gastroprotection with a PPI (omeprazole, pantoprazole) when the NSAID is taken for >2-4 weeks in patients with risk factors. Do not confuse NSAIDs and paracetamol — they are different classes; paracetamol does not protect the stomach, but it also does not irritate it.
Cardiovascular and renal
In 2013 the EMA issued a formal warning for diclofenac, recommending it be contraindicated in patients with established cardiovascular disease (heart failure NYHA II-IV, ischaemic heart disease, stroke, peripheral arterial disease). Naproxen remains the safest classic NSAID from a cardiovascular point of view, which is why it is preferred in at-risk patients.
On the renal side, NSAIDs reduce renal blood flow — a real risk in dehydration, treated hypertension, the elderly and diabetics. With the "NSAID + diuretic + ACE inhibitor" combination (the triple whammy) the risk of acute kidney injury is clearly described in the literature.
Absolute contraindications
- Active gastroduodenal ulcer or a history of NSAID-induced GI bleeding.
- Severe heart failure, recent myocardial infarction.
- Renal impairment with eGFR <30 mL/min.
- Third trimester of pregnancy — premature closure of the ductus arteriosus.
- Asthma worsened by aspirin or another NSAID.
CNAS reimbursement and availability in Romania
OTC ibuprofen (200 and 400 mg) and diclofenac gel are over the counter. The Rx forms (diclofenac 100 mg, injectable ketoprofen, celecoxib, etoricoxib) require a medical prescription and appear on CNAS List B or C for 50% reimbursement in certain indications. The reference price is set by CANAMED. On HartaFarmacii you can see the differences between Catena, Dona, Help Net, Farmacia Tei and Dr.Max.
Frequently asked questions
- Can I take ibuprofen on an empty stomach?
- Ideally not. With water, after a snack, you reduce irritation. At high doses or long treatments, ask the pharmacist about a PPI.
- Ibuprofen or paracetamol for fever?
- Both are effective. Paracetamol is first line in young children, in pregnancy and in patients with stomach problems. Ibuprofen has an anti-inflammatory bonus.
- Can I take ibuprofen and diclofenac together?
- No. All NSAIDs share the same mechanism — combining them increases toxicity without extra benefit.
- How long can I take an NSAID continuously?
- OTC: maximum 3 days for fever, 5 days for pain without medical advice. Longer — only on the doctor's instruction, with assessment of risk factors.
- Why did the diclofenac alert appear?
- Large studies (Coxib Trialists' Collaboration, 2013) showed a CV profile similar to the coxibs — increased risk of thrombotic events at therapeutic doses.
- Does cardiac aspirin (75-100 mg) belong here?
- It is a low-dose NSAID, used for its antiplatelet effect. Do not stop it without medical advice.
Topical NSAIDs: underused in Romania
Diclofenac gel (Voltaren Emulgel, Olfen Gel), ibuprofen cream (Dolgit Cream) and ketoprofen gel (Fastum Gel) are backed by serious clinical evidence: Cochrane meta-analyses (Derry et al., 2017) show efficacy comparable to the oral NSAID for knee osteoarthritis and local musculoskeletal conditions. With one major advantage: systemic absorption <10%, so gastric, renal and CV risk is much lower. For osteoarthritis of superficial joints (knees, fingers) — first choice before the oral ones.
Paediatrics: what is allowed and from what age
| Substance | From | Dose | Comment |
|---|---|---|---|
| Paracetamol | Birth | 10-15 mg/kg every 4-6h, max 60 mg/kg/day | First choice |
| Ibuprofen | 3-6 months / >5 kg | 5-10 mg/kg every 6-8h, max 30 mg/kg/day | Watch for dehydration |
| Aspirin | Only >16 years | — | Reye risk in viral illness |
| Ketoprofen, systemic diclofenac | Adolescent | — | Specific indications |
Oral suspensions (Nurofen for children, Paracetamol Sirop, Panadol Baby) are OTC. Watch for confusion between strengths (100 mg/5 mL vs. 200 mg/5 mL for ibuprofen) — a frequent cause of accidental overdoses reported to INSP.
Pregnancy and breastfeeding
Simple rules, in line with the ANMDMR SmPCs and EMA guidance:
- First-second trimester: paracetamol remains the first choice for pain and fever. NSAIDs (ibuprofen, naproxen) — limited use, low doses, short periods; recent observational data suggest a slightly increased risk of early pregnancy loss.
- Third trimester (over 20 weeks): NSAIDs are contraindicated — risk of oligohydramnios, fetal renal impairment and, above all, premature closure of the ductus arteriosus (FDA alert 2020, EMA).
- Breastfeeding: ibuprofen is compatible (minimal transfer into milk). Diclofenac, ketoprofen — short use is acceptable.
Storage and pharmaceutical form
Administration details significantly change the outcome:
- Gastro-resistant tablets (for example naproxen Naprosyn EC) — do not crush or chew; they protect the stomach by releasing in the small intestine.
- Oral suspensions (Nurofen suspension for children) — shake well before each dose; using the dosing syringe is more accurate than a teaspoon.
- Diclofenac patches (Flector Tissugel) — applied to intact skin, changed every 12 or 24 hours depending on the product; useful in tendinopathy.
- Diclofenac suppositories (Voltaren 50/100 mg) — useful in patients with acute gastric intolerance; absorption similar to oral for some formulations.
Common myths at the counter
- "If I take it with milk/yoghurt it won't hurt my stomach" — milk buffers the acid, but does not protect the mucosa from the NSAID mechanism (systemic COX-1 inhibition). A comforting illusion with no basis.
- "Ibuprofen is weaker than diclofenac" — at equivalent doses, the analgesic efficacy is comparable; the real difference is in the risk profile, not in "strength".
- "Voltaren gel is applied only on the skin, so it can't do harm" — absorption is small, but not zero. With very long courses over large areas, detectable systemic doses occur.
- "I take aspirin to thin my blood, but my stomach hurts — I'll add omeprazole" — correct, but discuss it with the doctor; sometimes clopidogrel is more appropriate.
Sources
- ANMDMR — SmPCs for ibuprofen, diclofenac, naproxen, celecoxib (anm.ro)
- EMA — Diclofenac safety review 2013; NSAIDs in pregnancy 2020
- BNF — NSAIDs prescribing notes
- NICE — guidance for analgesia in osteoarthritis
- Cochrane — Topical NSAIDs for chronic musculoskeletal pain (Derry et al., 2017)
- CNAS — reimbursed medicines lists B and C
- Ministry of Health — CANAMED