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FREENAK SP TABLETS

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FREENAK SP TABLETS

 Aceclofenac 100mg + Paracetamol 325mg + Serratiopeptidase 15 mg Salt Information :

Uses:

It is prescribed for fever, various kinds of pain and arthritis .

Side Effects:

Paracetamol: Nausea, allergic reactions, skin rashes, acute renal tubular necrosis. 

Aceclofenac: Diarrhoea, headache, vertigo, dizzies, nervousness, tinnitus, depression, drowsiness, insomnia; fever, angioedema, bronchospasm, rashes; blood dyscrasias. 

Potentially Fatal: Paracetamol: Very rare, blood dyscrasias (eg, thrombocytopaenia, leucopaenia, neutropaenia, agranulocytosis); liver damage. Aceclofenac: Severe GI bleeding; nephrotoxicity.

Drug Interactions:

Paracetamol: Reduced absorption of cholestyramine within 1 hr of administration. Accelerated absorption with metoclopramide. 

Aceclofenac: May increase the plasma concentrations of lithium and digoxin. Increased nephrotoxicity with diuretics. Serum-potassium should be monitored when used with potassium-sparing diuretics. May enhance activity of anticoagulants. May increase plasma methotrexate levels leading to toxicity if administered within 2-4 hr of methotrexate admin. Risk of convulsions with quinolones. 

Potentially Fatal: Paracetamol: Increased risk of liver damage in chronic alcoholics. Increased risk of toxicity with high doses or long term admin of barbiturates, carbamazepine, hydantoins, isoniazid, rifampin and sulfinpyrazone.

Contraindications:

Hypersensitivity. Moderate to severe renal or hepatic impairment; severe heart failure; pregnancy (third trimester).

Mechanism of Action:

Aceclofenac is a phenylacetic acid derivative that inhibits synthesis of the inflammatory cytokines interleukin-1b and tumour necrosis factor, and inhibits prostaglandin E2 production. It increases glycosaminoglycans (GAG) synthesis, the principal macromolecule of the extracellular matrix, which aids in repair and regeneration of articular cartilage. Thus, aceclofenac has +ve effects on cartilage anabolism combined with modulating effect of matrix catabolism.  

Paracetamol has analgesic and antipyretic action with weak anti-inflammatory activity. It produces analgesia by increasing pain threshold and antipyresis by acting on the hypothalamic heat-regulating centre.  

Absorption: Aceclofenac: Rapidly absorbed; almost 100% bioavailability; peak plasma levels reached about 1.25-3 hr after oral admin. 

Distribution: Aceclofenac: >99.7% bound to plasma proteins; distributes into synovial fluid. Paracetamol: Distributes throughout most fluids of the body.

Metabolism: Aceclofenac: Probably metabolised by CYP2C9; average plasma elimination half-life: 4-4.3 hr. Paracetamol: Mainly metabolised hepatically; plasma elimination half-life: 1-4 hr.  

Excretion: Aceclofenac: About two-thirds of the administered dose is removed in the urine, mainly as conjugated hydroxymetabolites. Paracetamol: Most metabolites are removed in the urine within 24 hr.

Special Precautions:

GI disease; renal or hepatic impairment; alcohol-dependent patients; asthma or allergic disorders; haemorrhagic disorders; hypertension; cardiac impairment. Elderly. Caution when driving or operating machinery. Monitor renal and hepatic function and blood counts during long term treatment. Persistently elevated hepatic enzyme levels may require drug withdrawal. Pregnancy, lactation

PARACETAMOL


Acetaminophen (USP) or paracetamol (INN), an acetanilide, is an analgesic and anti-pyretic drug indicated for temporary relief of fever and minor ache/pain.

Adult Dosage

Analgesia & feverOral 

  • 650–1000 mg tid/qid; maximum: 4000 mg/d
  • Extra strength: 1000 mg qid; maximum: 3000 mg/d
  • Extended release: 1300 mg tid; maximum: 3900 mg/d

IV

  • >50 kg, 1000 mg every 6 h, (or) 650 mg every 4 h as a single or repeated dose
  • Maximum single dose: 1000 mg
  • Maximum daily dose: 4000 mg/d
  • <50 kg, 15 mg/kg every 6 h or 12.5 mg/kg every 4 h as a single or repeated dose
  • Maximum single dose: 15 mg/kg or 750 mg
  • Maximum daily dose:  75 mg/kg/d or 3750 mg/24 h

Rectal

  • 650–1000 mg tid/qid
  • Maximum: 4000 mg/d

Pediatric Dosage

Analgesia & feverOral<12 y

  • 10–15 mg/kg/dose every 4–6 h
  • Maximum: 75 mg/kg/d

>12 y

  • 40–60 mg/kg/d qid
  • Maximum: >3.75 g/d

IV2–12 y, ≥13 y, <50 kg

  • 15 mg/kg every 6 h or 12.5 mg/kg every 4 h
  • Maximum single dose: 15 mg/kg or 750 mg
  • Maximum daily dose: 75 mg/kg/d or 3750 mg/d

≥13 y, >50 kg

  • 1000 mg every 6 h, or 650 mg every 4 h
  • Maximum single dose: 1000 mg
  • Maximum daily dose: 4000 mg/d

Rectal

  • Infants & children: Initial: 25–45 mg/kg in 4–5 divided doses
  • Maximum: 75 mg/kg/d for infants & 4000 mg/d in children in 4–5 divided doses

Postimmunization pyrexia Oral

  • 2–3 m: Maximum: 60 mg/kg/d in 3–4 divided doses

Dosage Adjustments

Hepatic impairment

  • Oral: Use with caution. Avoid chronic use in hepatic impairment.
  • Mild-to-moderate impairment: IV:  Use with caution in hepatic impairment or active liver disease
  • Severe impairment: Use is contraindicated

Renal impairmentModerate renal failure (GFR 10–50 mL/min)

  • Increase the dosing interval to every 6 h

Severe renal failure (GFR <10 mL/min) :

  • Increase the dosing interval to every 8 h

Indications

  • Osteoarthritis

Pregnancy & Lactation

  • Pregnancy: Category C-  Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
  • Lactation: Enters breast milk; use with caution

Mode of Action

Acetaminophen is a centrally acting analgesic and antipyretic with minimal anti-inflammatory properties. It reduces pain by inhibiting the central prostaglandin synthesis, specifically COX-2 and an elevation of the pain threshold. It reduces fever by inhibiting the release of prostaglandins in the CNS and by inhibition of endogenous pyrogens at the hypothalamic thermoregulatory centers.

Adverse Drug Reactions

Oral, Rectal

  • Frequency not defined
  • Anemia, increased ALP, ammonia, and bilirubin, analgesic nephropathy, blood dyscrasias, hypersensitivity reactions, nephrotoxicity, rash

IV>10%

  • Nausea, vomiting

1–10%

  • Anemia, abdominal pain, agitation, anxiety, atelectasis, constipation, dyspnea, diarrhea, edema, fatigue, hypervolemia, hypo/hypertension, headache, hypoalbuminemia, hypokalemia, hypomagnesemia, hypophosphatemia, hypoxia, insomnia, muscle spasms, oliguria, pruritus, pain in extremity, periorbital edema, pleural effusion, rash, stridor, trismus, tachycardia, wheezing

Interactions

  • Anti-convulsants: Anti-convulsants may increase the metabolism of acetaminophen. This may diminish the effect of acetaminophen and increase the risk of liver damage. Monitor therapy
  • Barbiturates: Barbiturates may increase the metabolism of acetaminophen. This may diminish the effect of acetaminophen and increase the risk of liver damage. Monitor therapy
  • Busulfan: Acetaminophen may increase the serum concentration of busulfan. Monitor therapy
  • Carbamazepine: Carbamazepine may increase the metabolism of acetaminophen. This may diminish the effect of acetaminophen and increase the risk of liver damage. Monitor therapy
  • Chloramphenicol: Acetaminophen may increase the serum levels of chloramphenicol
  • Cholestyramine: Cholestyramine may decrease the absorption of acetaminophen. Modify therapy
  • Dasatinib/imatinib: Acetaminophen may enhance the hepatotoxic effect of dasatinib/imatinib. Dasatinib/imatinib may increase the serum concentration of acetaminophen. Modify therapy
  • Isoniazid: Isoniazid may enhance the adverse/toxic effect of acetaminophen. Monitor therapy
  • Lomitapide: Acetaminophen may increase the serum concentration of lomitapide. Reduce lomitapide dose/modify therapy
  • Domperidone/metoclopramide: Domperidone/metoclopramide may increase the absorption of acetaminophen
  • Metyrapone: Metyrapone may increase the serum concentration of acetaminophen. Monitor therapy
  • Mipomersen: Acetaminophen may enhance the hepatotoxic effect of mipomersen. Monitor therapy
  • Peginterferon alfa-2b: Peginterferon alfa-2b may decrease the serum concentration of acetaminophen. Monitor therapy
  • Pimozide: Acetaminophen may increase the serum concentration of pimozide. Avoid concomitant use
  • Lidocaine/prilocaine: Acetaminophen may enhance the adverse/toxic effect of lidocaine/prilocaine. Monitor therapy in adults. Avoid concomitant use in pediatrics
  • Probenecid: Probenecid may increase the serum concentration of acetaminophen. Modify therapy
  • Sorafenib: Acetaminophen may enhance the hepatotoxic effect of sorafenib. Sorafenib may increase the serum concentration of acetaminophen. Modify therapy
  • Vitamin K antagonists: Acetaminophen may enhance the anti-coagulant effect of vitamin K antagonists. Monitor therapy

Contraindications & Warnings

  • Contraindicated in the following conditions  
  • Hypersensitivity to acetaminophen or any component of the formulation
  • Severe hepatic impairment or severe active liver disease
  • Increases the risk of the following  
  • Hepatotoxicity, risk is higher in alcoholics
  • Serious skin reactions
  • Hypovolemia
  • Severe renal impairment
  • Use with caution in patients with G6PD deficiency.

General Considerations

  • Advise patient to take with a full glass of water.
  • Advise patient to avoid alcohol
  • Advise patients who drink more than three alcoholic drinks a day to consult a healthcare professional prior to taking acetaminophen.
  • Advise patient that it is unsafe to take more than 4000 mg/day
  • In pediatric use, advise the parent or caregiver to closely read the drug label on the package to identify the concentration of the acetaminophen liquid (in mg/mL), dosage, and directions for use.

Monitoring Parameters

Monitor hepatic and renal function

Practice Insights

  • Use with caution in alcoholics; consider reducing the total daily dose as 4 g/d can cause toxicity in chronic alcoholics.
  • Use with caution in patients with G6PD deficiency as it causes hemolytic anemia.
  • Use a maximum of six suppositories/day.

ACECLOFENAC-

Aceclofenac is a nonsteroidal anti-inflammatory drug (NSAID's) used for the management of pain and inflammation in various arthritis conditions. In addition to anti-inflammatory action, it has analgesic, antipyretic and platelet-inhibitory actions.

Adult Dosage

Ankylosing spondylitis, osteoarthritis, & rheumatoid arthritisOral

  • 100 mg/d bid 
  • Sustained release : 200 mg/d

Pediatric Dosage

  • Safety and efficacy have not been established.

Dosage Adjustments

Hepatic Impairment

  • Reduce initial dose to 100 mg OD.

Renal Impairment

  • Avoid in patients with moderate to severe renal impairment.

Indications

  • Dental pain
  • Gout 
  • Postoperative pain 
  • Primary dysmenorrhea 

Pregnancy & Lactation

  • Pregnancy: Category C in 1st & 2nd trimester; Category D in 3rd trimester
  • Lactation: Excreted in breast milk; hence it is not recommended

Mode of Action

Aceclofenac is a nonsteroidal phenyl acetic acid derivative similar to Diclofenac. Like other NSAIDS, Aceclofenac is a COX inhibitor that decreases prostaglandin and leukotriene production, therefore inhibiting the inflammatory process.

Adverse Drug Reactions

Frequency not defined

  • Abdominal pain, blood dyscrasias, dyspepsia, dizziness, drug-induced GI disturbance, erythema, heartburn, hemoptysis, leukocytoclastic vasculitis, nephrotoxicity, nausea, pruritus, rashes, severe GI bleeding.

Interactions

  • Anti-coagulant drugs: Aceclofenac may enhance the anti-coagulant effect of anti-coagulant drugs
  • Anti-diabetic drugs: Aceclofenac may produce hypoglycemia/hyperglycemia with anti-diabetic drugs
  • Digoxin: Aceclofenac may increase the serum concentration of digoxin
  • Diuretics: Diuretics may enhance the risk of nephrotoxicity associated with aceclofenac
  • Lithium: Aceclofenac may increase the serum concentration of lithium
  • Non-steroidal anti-inflammatory drugs: Non-steroidal anti-inflammatory drugs may enhance the adverse/toxic effect of aceclofenac

Contraindications & Warnings

  • Contraindicated in the following conditions
  • Hypersensitivity to Aceclofenac or NSAIDs
  • Moderate to severe renal impairment
  • Pregnancy (3rd trimester)
  • Use with caution in the following
  • Hypertension or cardiac conditions
  • Preexisting infection 
  • History of peptic ulceration or GI bleeding
  • Liver dysfunction
  • Coagulation defects

General Considerations

  • Warn female patients to avoid use during pregnancy after 30-wk gestation. 
  • Advise patient to promptly report unexplained weight gain or edema.
  • Advise patient to take tablet with a full glass of water, food, or milk to minimize gastric irritation.
  • Advise patient to avoid taking Aspirin while taking drug.
  • Advise patient not to drink alcohol while taking this drug.
  • Advise patient to avoid the use of additional NSAIDs during therapy.

Monitoring Parameters

  • CBC, bleeding time 
  • BP, GI bleeding, or ulceration
  • Renal & hepatic function

Practice Insights

  • The drug should not be used for treating perioperative pain in the setting of CABG.
  • Increases the risk of thrombotic cardiovascular events and the risk increases with the duration of treatment.
  • Some studies have shown better GI tolerability profile with aceclofenac when compared to diclofenac.

SERRACIOPEPTIDASE-

It is a proteolytic enzyme (protease) produced by enterobacterium Serratia sp. used for painful conditions including back pain, osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, carpel tunnel syndrome, migraine headache, and tension headache. It is also used for conditions that involve pain and swelling (inflammation) including sinusitis, laryngitis, sore throat, ear infections, swelling after surgery, swelling of a vein with the formation of a blood clot (thrombophlebitis), and inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease. Some people use serrapeptase for heart disease and “hardening of the arteries” (atherosclerosis). Women use it for non-cancerous lumpy breasts (fibrocystic breast disease), and nursing mothers use it for breast pain caused by too much milk (breast engorgement). Other uses include treatment of diabetes, leg ulcers, asthma, and pus accumulation (empyema).

Adult Dosage

Inflammation & Edema 

  • Oral 
  • 5–10 mg tid

Pediatric Dosage

  • Safety and efficacy not established

Dosage Adjustments

  • Hepatic Impairment 
  • No data available
  • Renal Impairment 
  • No data available

Pregnancy & Lactation

  • Category unknown 
  • Excretion in breast milk is unknown; hence, not recommended 

Mode of Action

Serratiopeptidase helps to break down the protein which inturn helps to decrease inflammation and mucous.

Adverse Drug Reactions

  • Anorexia, diarrhea, epistaxis, GI disturbances, and skin rash

Interactions

  • Medications that slow downs blood clotting (Anticoagulant / Antiplatelet drugs) interacts with serrapeptase and might reduce its effects; concomitant use should be avoided.

Contraindications & Warnings

  • Contraindicated in the following
  • Hypersensitivity to Serratiopeptidase 
  • Use with caution in 
  • Severe hepatic & renal impairment

General Considerations

  • Advise patients to take with food to avoid GI upset

Monitoring Parameters

  • Inflammation & edema