Paracetamol adverse effects

Aspirin, paracetamol, and hydrocortisone are used to control febrile reactions of amphotericin. Patients with a history of adverse effects with amphotericin should be prophylactically treated with antipyretics and hydrocortisone. Antiemetics and pethidine also are used for the treatment of adverse effects of amphotericin. With sodium supplements and hydration therapy, damage to the kidney can be reduced. If conventional amphotericin is not well tolerated by the patient, colloidal carriers can be used as alternative options. Administration of amphotericin with a nephrotoxic drug, such as cyclosporin, may further increase toxicity. Diuretics and anticancer drugs should be avoided with amphotericin. 

Dextropropoxyphene Dextropropoxyphene, a drug of abuse, and any misuse or overdose of which causes intoxication if taken along with paracetamol or alcohol. The individual develops serious CNS depression leading to death.40-42 Adverse effects can be treated by gastric lavage and administration of activated charcoal and naloxone 43... 

Paracetamol is relatively free of adverse effects, but can cause hepato-toxicity in overdose. 

Adverse effects. Paracetamol is usually well-tolerated by the stomach because inhibition of prostaglandin synthesis in the periphery is weak allergic reactions and skin rash sometimes occur. Heavy, long-term daily use may predispose to chronic renal disease. 

Adverse effects are most commonly manifest as acute pancreatitis. The strongest association is with alcohol abuse. High plasma calcium, including that caused by hypervitaminosis D, and parenteral nutrition also increase the risk. Corticosteroids, didanosine, azathoipurine, diuretics (including thiazides and frusemide), sodium valproate, mesalazine and paracetamol (in overdose) have also been causally related. 

The concomitant use of paracetamol may increase the chance of adverse effects, especially erythema and urticaria (4). 

In one case jaundice occurred and rechaUenge with a single tablet of Parafon Forte (chlorzoxazone plus paracetamol) resulted in a dramatic reaction after 5 hours, with fever, chills, nausea, vomiting, and recurrence of icterus. Paracetamol on its own had no adverse effect in this case. 

A 20-year-old woman, who had previously taken paracetamol without adverse effects, took paracetamol 1 g and codeine 60 mg for a headache. After 3 hours she developed severe upper abdominal pain radiating to the back. The abdominal pain resolved within 24 hours of the administration of phloroglucinol and tiemonium. Her serum amylase activity was raised 3-fold and the serum lipase 15-fold. Other biochemical parameters, abdominal ultrasound, and an MRI scan were normal. Contrast-enhanced computed tomography showed pancreatic edema. 

Infusion-related adverse effects of gemtuzumab ozogamicin can be treated with a brief course of an intravenous glucocorticoid. Of 143 patients with refractory myeloid leukemia treated with gemtuzumab ozogamicin, 110 received paracetamol 650 mg orally with diphenhydramine 50 mg intravenously and 33 received the same premeditations plus methylprednisolone sodium succinate 50 mg intravenously before the infusion and repeated 1 hour later (1). There were grade 2 or worse infusion-related adverse events in 32 (29%) of the former, but in only one of the latter (3%). 

The general toxicity of interferon beta is very similar to that of interferon alfa (2), with no apparent differences between the two recombinant preparations with any route of injection (SEDA-20, 332) (3-6). In multiple sclerosis, fatigue and a transient flu-like syndrome responsive to paracetamol or the combination of paracetamol plus prednisone have been observed in about 60% of patients during the first weeks of treatment, and tachyphylaxis usually developed after several doses (7). Patients with chronic progressive disease are more likely to discontinue treatment because of adverse effects (8). 

A flu-like illness is the most common adverse effect of interferon beta. In an open, randomized study of the effects of paracetamol 1 g or ibuprofen 400 mg before and 6 hours after interferon beta injection on interferon beta-induced flu-like symptoms in 104 patients, the two drugs were equally effective (11). 

Nalbuphine has similar efficacy and incidence of adverse effects to tramadol and paracetamol (acetaminophen) (3). Dysrhythmias and coughing occurred more often with nalbuphine than fentanyl (4). 

The use of paracetamol as an antipyretic increased rapidly once phenacetin was no longer available and has received a boost more recently with wide acknowledgement of the role of aspirin as a causative agent in Reye s syndrome, resulting in the virtual disappearance of children s dosage forms of aspirin. While the incidence of adverse effects is reassuringly low, satisfaction must be tempered by appreciation of the relatively short duration of extensive clinical experience with paracetamol, its close relation to phenacetin, its low potency as an analgesic, and low public awareness of its potential adverse effects. 

An observational study, part of a population-based case-control study of dietary antioxidants and asthma, has shown an association between the regular use of paracetamol and the incidence of asthma and rhinitis in adults (10). After controlling for potential confounding factors the OR for asthma in daily users, compared with never users, was 2.38 (Cl = 1.22,4.64). Not unexpectedly, there was also an association in users and non-users of aspirin, strongest when cases with more severe disease were compared with controls. This adverse effect of paracetamol may be due to depletion of the antioxidant glutathione in the lungs. However, further studies are needed before paracetamol can be blamed for an increase in the prevalence and severity of asthma. 

Paracetamol crosses the placenta readily. However, there has been no published evidence of a teratogenic effect in the offspring of mothers who have taken paracetamol during pregnancy. A case of fetal death after a maternal overdose of paracetamol (30 g) has been described (SEDA-10, 73), but in another similar case, in which 22.5 g was taken in the 36th week, the fetus survived (SEDA-9, 96). PreUminary data from a longitudinal study have shown no adverse effects of therapeutic doses of paracetamol on either pregnancy or infant development (69). 

Skjetbred P, Lokken P. C eine added to paracetamol induced adverse effects but did not increase analgesia. BrJ Clin Pharmacol (1982) 14,539-43. 

Neomycin may increase the efficacy and the gastrointestinal adverse effects of acarbose. There is some indirect evidence that acarbose with alcohol may increase the hepatotoxicity of paracetamol (acetaminophen). Parafytic ileus has been reported in a Japanese patient treated with acarbose and promethazine, an an-timuscarinic drug. 

Paracetamol does not affect antibody production in response to influenza vaccination and appears to reduce its adverse effects. The pharmacokinetics of paracetamol do not appear to be affected by influenza vaccine. 

A single intramuscular dose of recombinant human interferon alfa-2a 18 million units was given to 8 healthy subjects alone, or after one day of either aspirin 650 mg every 4 hours, paracetamol 650 mg every 4 hours or prednisone 40 mg daily, for a total of 8 days. None of these additional drugs reduced the interferon adverse effects of fever, chills, headache, or myalgia. Only prednisone appeared to reduce one of the two measures of interferon activity. In a later similar study by the same research group, the effect of the same drugs and doses (started 3 days before the interferon) was evaluated with a lower dose of interferon alfa-2a (3 million units). When data for aspirin, paracetamol or prednisone was combined the... 

Taken together, the results of these two studies suggest that these drugs may reduce the flu-like adverse effects of interferon, perhaps more so at lower doses of interferon. The clinical relevance of the measures of antiviral activity of interferon is uncertain, so the disparate effects found with paracetamol and prednisone are unclear. 

In patients who may be highly susceptible to the adverse effects of traditional NSAIDs and COX-inhibitors, acetaminophen is a favorable alternative. Acetaminophen is a commonly used analgesic and antipyretic that is readily available in its oral form as an over-the-counter drug. It is also known as paracetamol or JV-acetyl-para-aminophenol (APAP), and is supplied in oral, rectal, and parenteral forms. Although the intravenous form has been available in various countries worldwide since 2002, it is currently still undergoing approval by the US Food and Drug Administration at the time of writing of this chapter. 

Lactation Breastfeeding by mothers taking codeine may be ill-advised, particularly if they are ultrarapid metaboUzers of codeine, in whom morphine is formed in large amounts, because of the risk of adverse effects on the baby [SEDA-31, 154], Reports of this association continue to appear. For example, a baby died after its breastfeeding mother took codeine and paracetamol, although the death could not be directly linked to codeine [41 ]. 

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