Ace500 mg

Ace 500 mg (also known as Acetaminophen) is one of the most widely used analgesic (pain-relieving) and antipyretic (fever-reducing) medicines in the world. It is suitable for adults, children, and infants and is available in numerous formulations for oral, rectal, and intravenous use. Ace 500 mg is indicated for the relief of the following conditions:

Fever and Infections

• Fever — reduction of elevated body temperature from any cause, including bacterial or viral infections
• Common cold and influenza — symptomatic relief of fever, body ache, and headache associated with cold and flu
• Post-vaccination fever in children — management of pyrexia and discomfort following immunization

Pain Relief

• Headache — including tension-type headache and migraine (mild to moderate)
• Toothache — dental pain relief
• Earache — pain associated with ear infections and inflammation
• Body ache — generalized musculoskeletal pain
• Myalgia — muscle pain associated with infections, exercise, or inflammation
• Neuralgia — nerve pain
• Dysmenorrhoea — painful menstruation (menstrual cramps)
• Sprains — soft tissue pain following minor injuries
• Colic pain — abdominal cramping pain
• Back pain — mild to moderate lower and upper back pain
• Post-operative pain — pain management following surgical procedures, as part of a multimodal analgesic regimen
• Postpartum pain — pain relief after childbirth
• Inflammatory pain — pain associated with inflammatory conditions

Musculoskeletal Conditions

• Rheumatic pain — pain associated with rheumatic conditions affecting joints and soft tissues
• Osteoarthritic pain and joint stiffness — Ace 500 mg is recommended as a first-line analgesic for mild to moderate osteoarthritis pain by major clinical guidelines worldwide

Note: Ace 500 mg is a pure analgesic and antipyretic. Unlike NSAIDs such as ibuprofen, it does not have significant peripheral anti-inflammatory activity and is therefore not appropriate as a primary treatment for inflammatory arthritis (e.g., rheumatoid arthritis). However, it is a preferred alternative for patients who cannot tolerate aspirin, NSAIDs, or other analgesics due to gastrointestinal sensitivity or contraindications.

Non-Opioid Analgesics / Antipyretics (Para-aminophenol derivatives)

Ace 500 mg (acetaminophen) is a non-opioid analgesic and antipyretic belonging to the para-aminophenol class of drugs. It is chemically distinct from NSAIDs and opioids, having its own unique mechanism of action that is still not fully understood despite decades of clinical use.

Mechanism of Action

Ace 500 mg exerts its effects primarily through central nervous system (CNS) mechanisms, rather than the peripheral mechanisms typical of NSAIDs.

Analgesic Effect (Pain Relief)

Ace 500 mg produces analgesia through peripheral blockade of pain impulse generation and through central inhibition of prostaglandin synthesis in the CNS, which raises the pain threshold. Unlike NSAIDs, it does not inhibit cyclooxygenase (COX) enzymes in peripheral tissues (such as the stomach, kidneys, and platelets) at therapeutic doses, which explains why it does not cause gastrointestinal irritation or platelet dysfunction.

COX Enzyme Inhibition

Ace 500 mg is thought to act by inhibiting all isoforms of the cyclooxygenase enzyme — including COX-1, COX-2, and a proposed variant called COX-3. However, unlike aspirin (which irreversibly blocks COX), Ace 500 mg appears to indirectly inhibit COX activity — and this inhibition is ineffective in the presence of high peroxide concentrations. This explains why:

• Ace 500 mg is effective in the CNS and endothelial cells (which have low peroxide levels)
• Ace 500 mg is NOT effective in platelets or immune cells (which have high peroxide levels)
• It does not impair platelet aggregation or cause significant GI mucosal injury

The COX-3 hypothesis proposes that Ace 500 mg selectively inhibits a splice variant of COX-1, now referred to as COX-3, which is predominantly expressed in the CNS. This may account for its central analgesic and antipyretic effects. However, the exact mechanism remains an active area of research.

Antipyretic Effect (Fever Reduction)

The antipyretic action of Ace 500 mg results from its direct effect on the heat-regulating centres of the hypothalamus. By inhibiting prostaglandin E2 (PGE2) synthesis in the hypothalamus — which is responsible for raising the thermoregulatory set point during infection or inflammation — Ace 500 mg restores the normal set point, promoting peripheral vasodilation and sweating, which dissipates body heat. Unlike aspirin, this action occurs without significant peripheral prostaglandin inhibition.

Pharmacokinetics

• Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract following oral administration. Bioavailability is approximately 63–89%. Peak plasma concentrations are achieved within 30 to 60 minutes after an oral dose (faster with fast-dissolving or actizorb formulations). Food may slightly delay absorption but does not significantly reduce overall bioavailability.
• Distribution: Widely and evenly distributed throughout most body fluids including the CNS. Volume of distribution is approximately 0.9 L/kg. Plasma protein binding is low (approximately 10–25%) at therapeutic concentrations, increasing to about 43% with toxic concentrations.
• Metabolism: Extensively metabolized in the liver — approximately 90–95% is conjugated to form inactive glucuronide (55–60%) and sulfate (30–35%) conjugates. A small proportion (5–10%) is oxidized by cytochrome P450 enzymes (primarily CYP2E1 and CYP3A4) to form a highly reactive, toxic intermediate — N-acetyl-p-benzoquinone imine (NAPQI). Under normal therapeutic conditions, NAPQI is rapidly detoxified by conjugation with hepatic glutathione, rendering it non-toxic. However, in overdose or in patients with depleted glutathione stores, NAPQI accumulates and causes severe hepatocellular necrosis.
• Half-life: Approximately 1.5 to 3 hours in healthy adults. Prolonged in neonates, patients with hepatic impairment, and in overdose.
• Elimination: Excreted primarily in the urine as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged Ace 500 mg. Excretion is essentially complete within 24 hours in patients with normal renal function.

Oral Tablets and Capsules

• Ace 500 mg tablets may be taken with or without food. Taking with food or milk may help if gastric discomfort occurs.
• Swallow tablets whole with a full glass of water.
• Extended-release tablets must NOT be crushed, broken, or chewed — this destroys the modified-release mechanism and may result in a rapid, potentially toxic dose.
• Do not take indigestion remedies (antacids) within 2 hours of taking Ace 500 mg as they may affect absorption.
• Space doses evenly throughout the day and observe the minimum dosing interval (at least 4 hours between standard doses; at least 6 hours between extended-release doses).
• Never take more than the recommended maximum daily dose, and never take two Ace 500 mg-containing products simultaneously.

Oral Suspension and Syrup

• Shake the bottle well before each use to ensure uniform distribution of the drug.
• Use the measuring device provided (oral syringe, measuring cup, or calibrated spoon) — do not use a regular household teaspoon as this may result in inaccurate dosing, particularly in infants.
• May be given with or without food.
• For pediatric suspensions: always confirm the concentration of the product being used (120 mg/5 ml) before calculating and administering the dose.

Paediatric Drops

• Use only the dropper supplied with the product to ensure accurate dosing.
• The dropper delivers 0.5 ml per dose — confirm the drop size and concentration before use.
• Do not exceed 5 doses in 24 hours and do not use for more than 5 consecutive days without medical advice.
• Can be given directly into the child's mouth or mixed with a small amount of formula, milk, or juice.

Suppositories (Rectal Administration)

• Suppositories are particularly useful when oral administration is not possible — for example, in children who are vomiting, nauseous, or uncooperative with oral medication.
• Wash hands before and after insertion.
• If the suppository is too soft, refrigerate it briefly (10–15 minutes) before use to firm it up.
• Remove the foil wrapping and insert the suppository, pointed end first, gently into the rectum.
• Keep the child still for a few minutes after insertion to allow adequate absorption.
• Store suppositories in a cool place below 25°C — excessive heat may cause them to melt.

IV Infusion (Hospital/Clinical Use Only)

• Ace 500 mg IV infusion (10 mg/ml, 100 ml) is indicated for patients who cannot receive oral medications — typically in the perioperative setting or in patients with nausea/vomiting.
• Administer by intravenous infusion over 15 minutes.
• Visually inspect the solution before use — discard if it is discolored or contains visible particles.
• Do not add other medications to the Ace 500 mg IV bottle or bag.
• Switch to oral Ace 500 mg as soon as the patient can tolerate oral medication.
• The minimum dosing interval for IV Ace 500 mg is 4 hours — do not administer more frequently than this.
• Monitor total daily dose from all sources carefully to avoid exceeding the maximum daily limit.

Although Ace 500 mg is generally considered to have fewer clinically significant drug interactions than NSAIDs, the following interactions require careful consideration:

Alcohol (Critical Interaction)

Concurrent or regular use of alcohol with Ace 500 mg significantly increases the risk of hepatotoxicity. Alcohol induces CYP2E1, the enzyme responsible for converting Ace 500 mg to its toxic metabolite NAPQI, and simultaneously depletes hepatic glutathione — reducing the liver's capacity to detoxify NAPQI. Even at doses within the normal therapeutic range, regular heavy alcohol use combined with Ace 500 mg increases hepatotoxicity risk substantially. Patients should be counseled to avoid alcohol during Ace 500 mg therapy.

Enzyme-Inducing Drugs (Anticonvulsants, Rifampicin)

Drugs that induce hepatic cytochrome P450 enzymes accelerate the metabolism of Ace 500 mg and increase NAPQI production. These include:

• Anticonvulsants: carbamazepine, phenobarbital (phenobarbitone), phenytoin, primidone
• Antituberculosis: rifampicin
• Herbal supplements: St John's Wort (Hypericum perforatum)

In patients taking these drugs, even normal doses of Ace 500 mg may carry greater hepatotoxicity risk — particularly at the upper end of the therapeutic range. These patients may also fail to achieve adequate therapeutic plasma Ace 500 mg concentrations due to increased clearance. A lower daily dose (e.g., maximum 2000–3000 mg/day) should be considered.

Oral Steroid Contraceptives

Chronic use of oral steroid contraceptives induces glucuronyl transferase activity, which increases the rate of Ace 500 mg metabolism and glucuronide conjugation, increasing first-pass metabolism and reducing systemic bioavailability. This may result in slightly lower plasma Ace 500 mg concentrations, potentially reducing its therapeutic effect.

Barbiturates

Barbiturates (e.g., phenobarbital) induce hepatic microsomal enzymes and may impair the ability to safely metabolize Ace 500 mg, increasing NAPQI formation and hepatotoxicity risk — particularly in overdose situations.

Tricyclic Antidepressants

Patients taking tricyclic antidepressants (e.g., amitriptyline, imipramine) may show diminished ability to metabolize large doses of Ace 500 mg safely, potentially increasing the risk of hepatotoxicity at supratherapeutic doses.

Warfarin and Other Anticoagulants

Regular use of high-dose Ace 500 mg (≥2 g/day for several days) may moderately enhance the anticoagulant effect of warfarin, increasing the risk of bleeding. The mechanism is thought to involve competitive inhibition of vitamin K-dependent coagulation factor synthesis. INR should be monitored more frequently in patients on warfarin therapy who start or increase Ace 500 mg use.

Probenecid

Probenecid inhibits the conjugation of Ace 500 mg with glucuronic acid in the liver, potentially doubling plasma Ace 500 mg concentrations. Patients taking Probenecid should use reduced doses of Ace 500 mg.

Domperidone and Metoclopramide

These prokinetic drugs increase the rate of gastric emptying and speed up Ace 500 mg absorption, resulting in faster onset of action. This interaction is not harmful but accelerates the therapeutic effect.

Cholestyramine

Cholestyramine binds Ace 500 mg in the GI tract, reducing its absorption. It should not be taken within 1 hour of Ace 500 mg. However, in Ace 500 mg overdose, cholestyramine may be used to reduce absorption if given early enough.

Ace 500 mg is one of the safest and best-tolerated analgesics and antipyretics when used at recommended doses for appropriate durations. Side effects at therapeutic doses are uncommon. However, the following adverse effects have been reported:

Common (At Therapeutic Doses)

Side effects at normal therapeutic doses are rare. The most commonly observed include:

• Nausea (mild, infrequent)
• Gastrointestinal discomfort in some patients — significantly less frequent than with NSAIDs

Skin and Hypersensitivity Reactions (Uncommon to Rare)

• Skin rash — ranging from mild maculopapular eruptions to urticaria
• Pruritus (itching)
• Angioedema — rare, but has been reported
• Life-threatening anaphylaxis — infrequently reported but recognized; may be more commonly associated with IV formulations. Discontinue Ace 500 mg immediately if signs of anaphylaxis develop (urticaria, bronchospasm, hypotension, facial swelling). Seek emergency medical care.

Hematological Effects (Rare)

• Thrombocytopenia — decreased platelet count; may cause unusual bleeding or bruising
• Leukopenia — decreased white blood cell count
• Neutropenia — decreased neutrophil count; may increase infection susceptibility
• Agranulocytosis — severe reduction in granulocytes; rare but serious
• Pancytopenia — reduction in all blood cell lines

Hepatic Effects (Dose-Related)

• Hepatotoxicity — the most clinically important adverse effect of Ace 500 mg, primarily associated with overdose but also possible at high therapeutic doses in high-risk patients. Characterized by elevated liver enzymes, jaundice, coagulopathy, and — in severe cases — hepatic failure. See Overdose Effects section for detailed information.
• Transient mild elevation of liver enzymes (ALT, AST) may occur in some patients on prolonged high-dose therapy.

Renal Effects (Rare, Long-Term High-Dose Use)

• Chronic high-dose Ace 500 mg use has been associated with analgesic nephropathy — characterized by chronic tubulointerstitial nephritis and renal papillary necrosis. This is rare at recommended doses but is a consideration with prolonged, high-dose use.
• Acute renal impairment may also occur in Ace 500 mg overdose.

Other Rare Effects

• Pancreatitis — reported rarely

Important safety reminder: Ace 500 mg is contained in many combination over-the-counter medicines for cold, flu, and pain. Patients must be advised not to take any other Ace 500 mg-containing products simultaneously to avoid unintentional overdose, which is a leading cause of acute hepatic failure.

Pregnancy

Ace 500 mg is generally considered the analgesic and antipyretic of first choice during pregnancy. Extensive epidemiological data from human pregnancy studies have shown no evidence of adverse effects on the fetus or newborn when Ace 500 mg is used at recommended doses for short durations. It does not carry the same risks as NSAIDs (which are contraindicated in the third trimester due to the risk of premature closure of the ductus arteriosus).

However, patients should always follow their doctor's advice regarding use during pregnancy. Recent observational studies have raised questions about the potential association between prolonged prenatal Ace 500 mg use and neurodevelopmental outcomes in children — this area of research is ongoing and inconclusive. As a general principle:

• Use the lowest effective dose for the shortest possible duration
• Avoid prolonged or continuous use without medical supervision
• Ace 500 mg remains the safest available option for pain and fever during all trimesters when treatment is necessary

Lactation

Ace 500 mg is excreted into human breast milk, but not in clinically significant amounts. Published data do not contraindicate breastfeeding during Ace 500 mg therapy at recommended doses. The estimated dose received by a breastfed infant is well below the pediatric therapeutic dose. Ace 500 mg is considered compatible with breastfeeding by international clinical guidelines and health organizations including the World Health Organization (WHO).

Critical Warning: Do Not Exceed the Maximum Daily Dose

Administration of Ace 500 mg in doses higher than recommended may result in severe hepatic injury, including the risk of life-threatening hepatotoxicity and death. The maximum recommended daily dose of Ace 500 mg must not be exceeded under any circumstances. This is particularly important because Ace 500 mg is present in hundreds of combination products — patients and caregivers must check all medications being taken simultaneously to ensure they are not inadvertently exceeding the safe daily limit.

Avoid Concurrent Ace 500 mg-Containing Products

Many over-the-counter products for cold, flu, allergy, and pain contain Ace 500 mg. Patients must be strongly advised not to take other Ace 500 mg-containing products concurrently. Accidental double dosing is a leading cause of Ace 500 mg-related hepatotoxicity and acute liver failure.

Hepatic Impairment

Ace 500 mg must be used with great caution in patients with:

• Hepatic impairment or active liver disease — reduce the total daily dose and use the lowest effective dose
• Non-cirrhotic alcoholic liver disease — maximum dose should not exceed 2 g/day
• Cirrhosis — Ace 500 mg is often still used cautiously at reduced doses (under physician supervision) as it is safer than NSAIDs in this population, but must not exceed 2 g/day

Renal Impairment

In severe renal impairment (creatinine clearance <30 mL/min), longer dosing intervals and a reduced total daily dose of Ace 500 mg are recommended. The minimum dosing interval should be extended to at least 6 hours. Regular monitoring of renal function is advised during prolonged therapy.

Alcoholism and Chronic Alcohol Use

The hazard of Ace 500 mg overdose and hepatotoxicity is substantially greater in individuals with alcoholism or chronic heavy alcohol use. This is because alcohol induces CYP2E1 (increasing NAPQI production) and depletes hepatic glutathione (reducing detoxification capacity). Even doses within the normal therapeutic range may carry hepatotoxicity risk in heavy alcohol users. Such patients should not use Ace 500 mg without medical supervision and should not exceed 2 g/day.

Malnutrition and Glutathione Depletion

Patients who are likely to have depleted hepatic glutathione stores are at significantly higher risk of Ace 500 mg-related liver damage — even at doses below the normal overdose threshold. Risk groups include:

• Patients with eating disorders (anorexia nervosa, bulimia)
• Patients with severe malnutrition or cachexia
• Patients with cystic fibrosis
• Patients with HIV/AIDS
• Patients who have been fasting or severely ill

Hypovolemia

Use caution when administering Ace 500 mg IV (and oral high doses) in patients with severe hypovolemia (e.g., due to dehydration, blood loss, or septic shock), as reduced hepatic and renal perfusion may impair drug metabolism and excretion, increasing toxicity risk.

Anaphylaxis Warning (IV Formulation)

Life-threatening anaphylaxis has been reported — particularly with IV Ace 500 mg. Discontinue IV Ace 500 mg immediately if any signs or symptoms of hypersensitivity or anaphylaxis develop (urticaria, rash, bronchospasm, angioedema, hypotension, or cardiovascular collapse). Emergency medical care must be available immediately when administering IV Ace 500 mg.

Children — 5-Day Rule

Ace 500 mg should not be given to children for pain for more than 5 consecutive days or for fever for more than 3 consecutive days without medical assessment. If symptoms persist, worsen, or new symptoms develop, a physician should be consulted.

Self-Medication and Monitoring

Patients on long-term Ace 500 mg therapy should have periodic monitoring of kidney function, liver function, and blood cell counts. Patients should avoid self-medicating for more than recommended periods without medical review.

Ace 500 mg overdose is one of the most common causes of drug-induced acute liver failure worldwide. It is a medical emergency requiring immediate treatment. Early intervention is critical — the effectiveness of antidotal therapy diminishes rapidly with time.

Threshold for Toxicity

• Adults with no risk factors: Liver damage is possible with ingestion of 10 g (20 tablets of 500 mg) or more in a single overdose
• At-risk patients (risk factors listed below): Liver damage may occur after ingestion of as little as 5 g or more

High-Risk Patients

The following conditions significantly lower the threshold for Ace 500 mg-induced hepatotoxicity:

• Patients on enzyme-inducing drugs: carbamazepine, phenobarbital (phenobarbitone), phenytoin, primidone, rifampicin, St John's Wort
• Regular excess alcohol consumption
• Conditions causing glutathione depletion: eating disorders, cystic fibrosis, HIV infection, starvation, cachexia

Symptoms of Overdose — Timeline

First 24 Hours

• Pallor and general malaise
• Nausea, vomiting, and anorexia
• Abdominal pain — particularly right upper quadrant
• Patients may appear relatively well initially — this can create a false sense of security

12–72 Hours

• Liver damage becomes apparent — rising liver enzymes (ALT, AST), elevated INR, elevated bilirubin
• Abnormalities of glucose metabolism and metabolic acidosis
• Jaundice may develop

Severe Overdose (72–96+ Hours)

• Hepatic failure — progressive liver necrosis
• Encephalopathy (confusion, disorientation, coma)
• Haemorrhage and coagulopathy (elevated PT/INR)
• Severe hypoglycaemia
• Cerebral oedema
• Acute renal failure with acute tubular necrosis — suggested by loin pain, haematuria, and proteinuria; may develop even in the absence of severe liver damage
• Cardiac arrhythmias
• Pancreatitis
• Death — in fulminant hepatic failure without liver transplantation

Emergency Management of Ace 500 mg Overdose

Immediate medical attention is essential. Do not wait for symptoms to develop before seeking treatment.

1. Activated charcoal: Should be considered if the patient presents within 1 hour of ingestion and can protect their airway. It reduces GI absorption of Ace 500 mg.
2. Plasma Ace 500 mg concentration: Measure at 4 hours or later after ingestion — concentrations measured before 4 hours are unreliable. Plot on the Rumack-Matthew nomogram to assess hepatotoxicity risk and guide N-acetylcysteine therapy.
3. N-Acetylcysteine (NAC) — specific antidote: The antidote of choice for Ace 500 mg overdose. NAC works by:
   • Replenishing hepatic glutathione stores
   • Directly detoxifying NAPQI
   NAC may be used up to 24 hours after ingestion, but maximum protective effect is obtained if started within 8 hours. The effectiveness of NAC declines sharply after 8 hours post-ingestion. Administer IV NAC according to the established dosage protocol (Prescott regimen or modified infusion regimen).
4. Oral Methionine: May be used as an alternative to NAC for patients in remote areas without IV access, provided vomiting is not a problem.
5. Hepatic monitoring: Monitor liver function tests (ALT, AST, INR, bilirubin), blood glucose, renal function, and electrolytes.
6. Specialist referral: Management of patients with serious hepatic dysfunction beyond 24 hours should be discussed with a Poisons Information Centre (e.g., NPIS in the UK) or a specialized liver unit — liver transplantation may be considered for fulminant hepatic failure.

If Ace 500 mg overdose is suspected, contact emergency services or a poison control center immediately. Do not wait for symptoms to develop.

• Store tablets, capsules, and dry powder/granules below 25°C–30°C, in a cool, dry place away from direct light, heat, and moisture.
• Keep all formulations out of the reach of children. Ace 500 mg overdose in children can be fatal — safe storage is critically important.
• Do not use any formulation after the expiry date printed on the packaging.
• Oral suspension (after opening): Store at room temperature below 25°C. Use within the period stated on the label after opening (usually 3–4 weeks). Do not refrigerate unless the label specifies this — chilling may thicken the suspension. Shake well before each use.
• Suppositories: Store below 25°C in a cool place. High ambient temperatures (common in Bangladesh's climate) may soften or melt suppositories — if this occurs, refrigerate briefly before use. Do not freeze.
• IV infusion solution: Store below 25°C, protected from light, in the original packaging. Do not freeze. Once opened, administer immediately and discard any unused portion — do not store opened IV bottles for later use.
• Store all Ace 500 mg-containing products securely, away from children's reach, in a locked or high cabinet. Accidental ingestion by children is a common pediatric medical emergency.

Pediatric Patients

The safety and effectiveness of Ace 500 mg IV for acute pain and fever have been established in pediatric patients aged 2 years and older, supported by evidence from well-controlled clinical studies. For children under 2 years, IV Ace 500 mg may be used under close medical supervision when no safer oral alternative is feasible. Oral and rectal Ace 500 mg formulations are widely used in infants and children of all ages. Dosing must be weight-based and age-appropriate — always calculate the correct dose based on the child's current weight. Never give adult-strength tablets to children under 12 without specific medical guidance.

Elderly Patients

No significant overall differences in safety or effectiveness have been identified between elderly and younger adult patients when Ace 500 mg is used at recommended doses. However, elderly patients are more likely to have reduced renal function and hepatic reserve, increasing their susceptibility to adverse effects with prolonged or high-dose use. The lowest effective dose should be used, and therapy should be periodically reviewed. Regular monitoring of renal function, liver function, and blood pressure is advisable in elderly patients on long-term Ace 500 mg therapy.

Patients with Hepatic Impairment

Ace 500 mg is contraindicated in patients with severe hepatic impairment or severe active liver disease. In patients with mild to moderate hepatic impairment, Ace 500 mg may be used cautiously at reduced doses (typically maximum 2 g/day). The dosing interval should be extended to allow more time between doses. Regular liver function monitoring is essential during any course of Ace 500 mg in patients with hepatic disease. Ace 500 mg remains preferable to NSAIDs in patients with hepatic impairment and ascites (where NSAIDs cause significant renal risks), but must be dose-adjusted.

Patients with Renal Impairment

In cases of severe renal impairment (creatinine clearance <30 mL/min), longer dosing intervals (minimum every 6 hours) and a reduced total daily dose are recommended to prevent accumulation of Ace 500 mg metabolites. Ace 500 mg is generally preferred over NSAIDs in patients with renal impairment, as NSAIDs can precipitate acute kidney injury. Renal function should be regularly monitored during long-term Ace 500 mg therapy in patients with pre-existing kidney disease.