Astefor (Codeine,Ibuprofen)

Astefor (Codeine,Ibuprofen) Uses, Dosage, Side Effects, Food Interaction and all others data.

The relief of pain (analgesia) is a primary goal for enhancing the quality of life of patients and for increasing the ability of patients to engage in day to day activities. Codeine, an opioid analgesic, was originally approved in the US in 1950 and is a drug used to decrease pain by increasing the threshold for pain without impairing consciousness or altering other sensory functions. Opiates such as codeine are derived from the poppy plant, Papaver somniferum (Papaveraceae).

Codeine is utilized as a central analgesic, sedative, hypnotic, antinociceptive, and antiperistaltic agent, and is also recommended in certain diseases with incessant coughing.

General effects

Ibuprofen is a non-selective inhibitor of cyclooxygenase, an enzyme invovled in prostaglandin synthesis via the arachidonic acid pathway. Its pharmacological effects are believed to be due to inhibition cylooxygenase-2 (COX-2) which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the more pharmacologically active enantiomer.

Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials.

The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region.

The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen.

Astefor (Codeine,Ibuprofen)
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Astefor (Codeine,Ibuprofen)
Generic	Codeine + Ibuprofen
Type
Therapeutic Class
Manufacturer
Available Country	Spain
Last Updated:	September 19, 2023 at 7:00 am

Uses

Codeine is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

Codeine sulfate is a form of this drug that is commonly used. It is available in tablet form and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate .

The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above , .

Ibuprofen is used

For the treatment of sign and symptoms of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and other non-rheumatoid arthropathies,
For the treatment of non-articular rheumatic conditions, such as frozen shoulder, bursitis, tendinitis, tenosynovitis and low back pain,
For the treatment of soft tissue injuries such as sprain, strain and post operative pain
For the treatment of dysmenorrhoea,
For the treatment of dental pain.
For the treatment of cold & fever.

Astefor (Codeine,Ibuprofen) is also used to associated treatment for these conditions: Common Cold, Cough, Flu caused by Influenza, Mild pain, Pain, Severe Pain, Dry cough, Moderate Pain, Upper respiratory symptoms, Airway secretion clearance therapyAnkylosing Spondylitis (AS), Common Cold, Cystic Fibrosis (CF), Fever, Gastric Ulcer, Gouty Arthritis, Headache, Insomnia, Juvenile Idiopathic Arthritis (JIA), Menstrual Distress (Dysmenorrhea), Migraine, Mild pain, Nasal Congestion, Osteoarthritis (OA), Pain, Pain, Acute, Pain, Inflammatory, Patent Ductus Arteriosus (PDA), Pericarditis, Primary Dysmenorrhoea, Rheumatoid Arthritis, Severe Pain, Sinus pressure, Mild to moderate pain, Minor aches and pains, Moderate Pain

How Astefor (Codeine,Ibuprofen) works

Codeine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug. Codeine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system , . The analgesic properties of codeine are thought to arise from its conversion to Morphine, although the exact mechanism of analgesic action is unknown at this time , .

The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway.

Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.

Dosage

Astefor (Codeine,Ibuprofen) dosage

Oral Administrations-

For Children:

20 mg per kg body weight daily in divided doses. In children weighing less than 30 kg the total daily dosage should not exceed 500 mg. If gastrointestinal disturbances occur Ibuprofenshould be given with food or milk.
1-2 years: 1/2 tea spoonful (2.5 ml) 3-4 times daily;
3-7 years: 1 tea spoonful (5 ml) 3-4 times daily;
8-12 years: 2 tea spoonful (10 ml) 3-4 times daily. Ibuprofenis not recommended for children under 1 year.

For adult:

For arthritic pain: The dosage range is from 0.9 to 2.4 g per day. The usual dose is 400 mg, 3-4 times per day, preferably after food. The dose may be raised to a maximum of 2.4 g daily depending on the severity of symptom at the time of initiating drug therapy or as patients fail to respond. After a satisfactory response has been achieved the patients dose should be reviewed and adjusted as required and tapered gradually.
For mild to moderate pain: 400 mg 6 hourly or as demanded by the condition.
For dysmenorrhoea: 400 mg every 4 hours or as demanded by the condition.

Topical Administrations-

Pain and inflammation associated with musculoskeletal and joint disorder: As 5% cream, foam, gel, spray soln or 10% gel: Apply onto affected area.

Side Effects

Usually Ibuprofen has a low incidence of side effects. The most frequent side effects are gastrointestinal disturbances. Peptic ulceration and gastrointestinal bleeding have occasionally been reported. Other side effects include headache, dizziness, nervousness, skin rash, pruritus, drowsiness, insomnia, blurred vision and other ocular reactions, hypersensitivity reaction, abnormal liver function test, impairment of renal function, agranulocytosis and thrombocytopenia.

Toxicity

Oral LD50: 427 mg kg-1 (rat) .

Overdose/toxicity

Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal , .

Teratogenic effects

This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Codeine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus .

Codeine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose . Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison .

Nonteratogenic effects

Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment .

Codeine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day .

The use in breastfeeding/nursing

Codeine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants .

The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).

The reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig.

Precaution

Ibuprofen should be given with caution to patients with bleeding disorders, cardiovascular diseases, peptic ulceration or a history of such ulceration and in those who are receiving coumarin anticoagulants and in patients with renal or hepatic impairment.

Interaction

Increased risk of GI bleeding with warfarin, corticosteroids, SSRIs and aspirin. May reduce the natriuretic effects of diuretics. Reduced antihypertensive effect of ACE inhibitors and angiotensin II receptor antagonists. May increase toxicity of lithium and methotrexate. Increased nephrotoxicity with ciclosporin and tacrolimus.

Volume of Distribution

Apparent volume of distribution: about 3-6 L/kg, showing an extensive distribution of the drug into tissues .

The apparent volume of distribution of ibuprofen is of 0.1 L/kg.

Elimination Route

Absorption

Codeine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration .

Food Effects

When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine .

Steady-state concentration

The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours .

It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption.

When orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract. The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration.

Half Life

Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours .

The serum half-life of ibuprofen is 1.2-2 hours. In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours.

Clearance

Renal clearance of codeine was 183 +/- 59 ml min-1 in a clinical study .

Renal impairment may decrease codeine clearance .

The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage.

Elimination Route

About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine .

The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine .

Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose. The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose.

In summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment.

Pregnancy & Breastfeeding use

Ibuprofen is not recommended during pregnancy or for use in nursing mothers.

Contraindication

Ibuprofen should not be given to patients with hypersensitivity to lbuprofen and to individuals who show nasal polyps, angioedema, bronchospastic reactivity to aspirin or other non-steroidal anti-inflammatory drug. Ibuprofen is contraindicated in patients with active or previous peptic ulceration & gastro-intestinal ulceration or bleeding.