Pruritus drug-induced

Frequent ADRs, which occur in about 5% of drug-induced side effects (study in hospitalized patients) In 5-13% of cutaneous ADRs, pruritus occurs without skin symptoms, although the incidence varies with different drugs (e.g. opiate-induced pruritus in 50-90% of patients).

Drug-induced pruritus can be triggered by a wide range of drugs. This ranges from antihypertensives to antiepileptic and antineoplastic substances.

Drug-induced pruritus can be acute (duration < 6 weeks) or chronic (duration > 6 weeks), localized or generalized.

The connection between the duration of medication and the first occurrence of chronic itching (> 6 weeks) is still unclear. With acute itching (< 6 weeks) the connection is usually clear.

Acute itching (< 6 weeks):

• Immunological reactions
  • Immunological type I reactions
  • Immunological type IV reactions
• Non-immunological reactions
  • Drug-induced histamine release (tramadol, codeine, cocaine, morphine, fentanyl, muscle relaxants, X-ray contrast agent)
  • Disorders in the u- and kappa-opioid systems due to morphines
  • Enzyme inhibition, e.g. cycloxigenase I inhibition by NSA (leads to an excessive formation of leukotrienes from arachidonic acid in mast cells and eosinophilic leukocytes)
  • Aquagenic pruritus due to e.g. antimalarial drugs or the antidepressant bupropion)
  • Phototoxic and photoallergic reactions (see photoallergen below)

Chronic itching (> 6 weeks)

• Skin diseases provoked by medication (e.g. psoriasis due to beta blockers)
• Aquagenic pruritus due to e.g. antimalarials
• Phototoxic and photoallergic reactions
• Cholestasis-inducing drugs (oral contraceptives, captopril, valproic acid, erythromycin, sulfonamides, minocycline)
• Hepatotoxicity caused by drugs
• Sebostasis through medication
• Pruritus under chemotherapy (combination of sorafinib with interferon alpha, sunitinib, ipilimumab, EGFR-inhibitors (50% pruritus), various types of cancer) MEK inhibitors)
• HAES-induced pruritus

Medications that commonly trigger pruritus:

• Drugs causing pruritus
• Acute Pruritus:
  • Opioids and antagonists: codeine, fentanyl, levomethadone, morphine and derivatives, naloxone, pentazocine, sufentanil (up to 25%), tramadol
  • Antimalarials: chloroquine: (up to 90% of patients), hydroxychloroquine (1.5%), amodiaquine (23.8%)
  • Antihypertensives: Amlodipine
  • Chemotherapeutic agents: e.g. paclitaxel, carboplatin (17%), cisplatin, mitomycin C, gemcitabine, imatinib, erlotinib, rituximab
  • Disinfectant for dialysis machines: ethylene oxide
  • TNF inhibitors: etanercept, infliximab
  • Alpha-receptor blockers for prostatic hyperplasia: e.g. tamsulosin
  • Uricostatic drugs: allopurinol
• Chronic pruritus (> 6 weeks duration)
• ACE inhibitors: captopril, enalapril, lisinopril
• Angiotensin-2 receptor blockers: valsartan, losartan, candesartan
• Antiarrhythmics: e.g. amiodarone, disopyramide, flecainide
• Antibiotics: amoxicillin, ampicillin, cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, clarithromycin, clindamycin, co-trimoxazole, erythromycin, gentamycin, metronidazole, minocycline, ofloxacin, penicillin, tetracycline
• antidepressants: amitryptyline, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, lithium salts, maprotiline, mirtazapine, nortriptyline, paroxetine, sertraline
• antidiabetics: glimepiride, metformin, tolbutamide
• antihypertensives: clonidine, doxazosin, hydralazine, methyldopa, minoxidil, prazosin, reserpine
• anticonvulsants: carbamazepine, clonazepam, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate, valproic acid
• Anti-inflammatories: e.g. acetylsalicylic acid, celecoxib, diclofenac, ibuprofen, indometacin, ketoprofen, naproxen, piroxicam
• beta blockers: e.g. acebutolol, atenolol, bisoprolol, metoprolol, nadolol, pindolol, propranolol
• Bronchodilators, broncholytics: aminophylline, doxapram, ipratropium bromide, salmeterol, terbutaline
• Calcium antagonists: amlodipine, diltiazem, felodipine, isradipine, nifedipine, nimodipine, nisoldipine, verapamil
• diuretics: amiloride, furosemide, hydrochlorothiazide, spironolactone, triamterene
• Hormones: clomiphene, danazol, oral contraceptives, estrogens, progesterones, steroids, testosterone and derivatives, tamoxifen
• immunosuppressants: cyclophosphamide, cyclosporine, methotrexate, mycophenolate mofetil, tacrolimus (up to 36%), thalidomide
• lipid-lowering agents: clofibrate, fenofibrate, fluvastatin, lovastatin, pravastatin, simvastatin
• neuroleptics: chlorpromazine, haloperidol, risperidone
• plasma expanders, circulatory stimulants: HAES (hydroxyethyl starch), pentoxifylline
• tranquilizers: alprazolam, chlordiazepoxide, lorazepam, oxazepam, prazepam
• Uricostats, uricosurics: allopurinol, colchicine, probenecid, tiopronin

Drug-induced pruritus often manifests itself on clinically inconspicuous skin; scratch marks are found less frequently.

Targeted patient anamnesis; all current medication as well as medication taken in the immediate past must be recorded. In addition, infusions, hospital stays, operations and emergency medical services (e.g. HAES) are to be taken into account, as well as over-the-counter homoeopathics and vitamins.

General therapy measures do not exist. The most important principle is to identify the cause in question. Accompanyingly, a re-fattening basic therapy is recommended, if necessary with the addition of polidocanol.

1. AWMB Guideline (2012) Pruritus. Reg.No.: 013-048 based on version 2.1, as of 27.01.2011
2. Bifby M et al (1986) Drug induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients. 1975-1982. JAMA 256: 3356-3363
3. Maleki K et al (2014) Drug-induced pruritus. Dermatologist 65: 436-442
4. Weishaar E et al (2012) European guideline on chronic pruritus. Acta Dermatovenereol 92: 563-581