Acupain

Acupain Uses, Dosage, Side Effects, Food Interaction and all others data.

Acupain is a centrally acting synthetic analgesic compound. It inhibits the re uptake of neurotransmitters- serotonin and noradrenaline. Thus it modifies the transmission of pain impulses by activating both descending serotonergic pathways and noradrenergic pathways involved in analgesia. The analgesic effects of Acupain are mediated via stimulation of mu-opioid receptors and indirect modulation of central monoaminergic inhibitory pathways.

Acupain modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.

Apart from analgesia, tramadol may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids.

Central Nervous System

Trade Name Acupain
Availability Prescription only
Generic Tramadol
Tramadol Other Names Tramadol, Tramadolum
Related Drugs Buprenex, Subutex, aspirin, ibuprofen, acetaminophen, duloxetine, naproxen, diclofenac, Tylenol, oxycodone
Weight 10mg, 30mg/ml, 10mg/ml, 30mg, 20mg/ml
Type Injection, Tablet, Im/iv Injection
Formula C16H25NO2
Weight Average: 263.3752
Monoisotopic: 263.188529049
Protein binding

About 20% of the administered dose is found to bind to plasma proteins. Protein binding appears to be independent of concentrations up to 10μg/mL. Saturation only occurs at concentrations outside of the clinical range.

Groups Approved, Investigational
Therapeutic Class Opioid analgesics
Manufacturer Eden Pharmaceuticals Ltd, Beacon Pharmaceuticals Ltd, Ibn-sina Pharmaceuticals Ltd
Available Country India, Bangladesh
Last Updated: September 19, 2023 at 7:00 am
Acupain
Acupain

Uses

Acupain is used for the treatment of moderate to severe painful conditions. These include: Postoperative pain, Colic and spastic pain, Cancer pain, Joint pain, Neck and back pain & Pain associated with osteoporosis.

Acupain is also used to associated treatment for these conditions: Pain, Acute, Premature Ejaculation, Severe Pain, Acute, moderate, severe Pain, Moderate Pain

How Acupain works

Acupain is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to codeine and morphine. Acupain binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with 6000-fold less affinity than morphine.

Acupain exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the μ opioid receptor while (+)-tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake. These pathways are complementary and synergistic, improving tramadol's ability to modulate the perception of and response to pain.

In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding.

Acupain has also been shown to affect a number of pain modulators including alpha2-adrenoreceptors, neurokinin 1 receptors, the voltage-gated sodium channel type II alpha subunit, transient receptor potential cation channel subfamily V member 1 (TRPV1 - also known as the capsaicin receptor), muscarinic receptors (M1 and M3), N-methyl-D-aspartate receptor (also known as the NMDA receptor or glutamate receptor), Adenosine A1 receptors, and nicotinic acetylcholine receptor.

In addition to the above neuronal targets, tramadol has a number of effects on inflammatory and immune mediators involved in the pain response. This includes inhibitory effects on cytokines, prostaglandin E2 (PGE2), nuclear factor-κB, and glial cells as well as a change in the polarization state of M1 macrophages.

Dosage

Acupain dosage

Capsule or Tablet: Usual doses are 50 to 100 mg every four to six hours. For acute pain an initial dose of 100 mg is required. For chronic painful conditions an initial dose of 50 mg is recommended. Subsequent doses should be 50 to 100 mg administered 4-6 hourly. The dose level and frequency of dosing will depend on the severity of the pain.The total daily dosage by mouth should not exceed 400 mg.

Sustained Release Capsule or Tablet: One SR capsule or tablet every 12 hours, for example first one in the morning and then at the same time in the evening. The number of capsules taken at a time will depend upon severity of pain, but it should not be taken more frequently than every 12 hours.The total daily dosage by mouth should not exceed 400 mg.

Injection: A dose of 50-100 mg may be given every 4 to 6 hours by intramuscular or by intravenous infusion. For the treatment of postoperative pain,the initial dose is 100 mg followed by 50 mg every 10 to 20 minutes if necessary to a maximum of 250 mg in the first hour. Thereafter, doses are 50 to 100 mg every 4 to 6 hours up to a total daily dose of 600 mg.

Suppository: Acupain suppository should be administered rectally. For adults usual dose is 100 mg Acupain Hydrochloride 6 hourly. In general, 400 mg Acupain Hydrochloride (4 Acupain suppository) per day sufficient. However, for the treatment of Cancer pain and severe pain after operations much higher daily doses can be used.

Side Effects

Commonly occurring side-effects are dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting, pruritus, CNS stimulation, asthenia, sweating, dyspepsia, dry mouth, diarrhoea.

Less commonly occurring side-effects include malaise, allergic reaction, weight loss, vasodilatation, palpitations, abdominal pain, anorexia, flatulence, GI bleeding, hepatitis, stomatitis etc.

Toxicity

The reported LD50 for tramadol, when administered orally in mice, is 350 mg/kg.

In carcinogenic studies, there are reports of murine tumors which cannot be concluded to be carcinogenic in humans. On the other hand, tramadol showed no evidence to be mutagenic in different assays and does not have effects on fertility. However, there are clear reports of embryotoxicity and fetotoxicity.

Precaution

Respiratory depression: When large doses of tramadol are administered with anaesthetic with anaesthetic medications or alcohol, respiratory depression may result. Therefore, tramadol should be administered cautiously in patients at risk for respiratory depression.

Opioid dependence: Acupain is not recommended for patients who are dependent on opioids.

Concomitant CNS depressants: Acupain should be used with caution and in reduced dosages when administering to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, phenothiazines, tranquilizers or sedative hypnotics.

Concomitant MAO inhibitors: Acupain should be used with great caution in patients taking MAO inhibitors, since tramadol inhibits the uptake of norepinephrine and serotonin.

Acupain should be used with caution in patients with increased intracranial pressure or head injury and patients with acute abdominal conditions.

Interaction

In general, physician need not be concerned about drugs interacting with Acupain. The monoamine oxidase (MAO) inhibitors represent the only drug class not recommended for combination with Acupain. Concomitant administration of carbamazepine with Acupain causes a significant increase in Acupain metabolism and it requires to increase the dose of Acupain.

Food Interaction

  • Avoid alcohol. Co-administration of alcohol may potentiate the CNS effects of tramadol.
  • Take with or without food. Co-administration of food does not affect pharmacokinetics.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Volume of Distribution

The volume of distribution of tramadol is reported to be in the range of 2.6-2.9 L/kg. Acupain has high tissue affinity; the total volume of distribution after oral administration was 306L and 203L after parenteral administration. Acupain crosses the blood-brain barrier with peak brain concentrations occurring 10 minutes following oral administration. It also crosses the placental barrier with umbilical concentrations being found to be ~80% of maternal concentrations.

Elimination Route

Oral Administration

Acupain is administered as a racemate, with both the [-] and [+] forms of both tramadol and the M1 metabolite detected in circulation. Following administration, racemic tramadol is rapidly and almost completely absorbed, with a bioavailability of 75%. This difference in absorption and bioavailability can be attributed to the 20-30% first-pass metabolism. Peak plasma concentrations of tramadol and the primary metabolite M1 occur at two and three hours, respectively. Following a single oral dose of 100mg of tramadol, the Cmax was found to be approximately 300μg/L with a Tmax of 1.6-1.9 hours, while metabolite M1 was found to have a Cmax of 55μg/L with a Tmax of 3 hours.

Steady-state plasma concentrations of both tramadol and M1 are achieved within two days of dosing. There is no evidence of self-induction. Following multiple oral doses, Cmax is 16% higher and AUC is 36% higher than after a single dose, demonstrating a potential role of saturable first-pass hepatic metabolism in increasing bioavailability.

Intramuscular Administration

Acupain is rapidly and almost completely absorbed following intramuscular administration. Following injection of 50mg of tramadol, Cmax of 166μg/L was found with a Tmax of 0.75 hours.

Rectal Administration

Following rectal administration with suppositories containing 100mg of tramadol, Cmax of 294μg/L was found with a Tmax of 3.3 hours. The absolute bioavailability was found to be higher than oral administration (77% vs 75%), likely due to reduced first-pass metabolism with rectal administration compared to oral administration.

Half Life

Acupain reported a half-life of 5-6 hours while the M1 metabolite presents a half-life of 8 hours.

Clearance

In clinical trials, the clearance rate of tramadol ranged from 3.73 ml/min/kg in renal impairment patients to 8.50 ml/min/kg in healthy adults.

Elimination Route

Acupain is eliminated primarily through metabolism by the liver and the metabolites are excreted primarily by the kidneys, accounting for 90% of the excretion while the remaining 10% is excreted through feces. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

The mean terminal plasma elimination half-lives of racemic tramadol and racemic M1 are 6.3 ± 1.4 and 7.4 ± 1.4 hours, respectively. The plasma elimination half-life of racemic tramadol increased from approximately six hours to seven hours upon multiple dosing.

Pregnancy & Breastfeeding use

Safe use of Acupain in pregnancy has not been established. Acupain has been shown to cross the placenta. There are no adequate and well-controlled studies in pregnant women. Therefore, Acupain should be used during pregnancy only if the potential benefit justifies the risk to the foetus. Acupain Hydrochloride should not be administered during breast feeding as Acupain and its metabolites have been detected in breast milk.

Contraindication

Acupain is contraindicated in persons having hypersensitivity to this drug. It is also contraindicated in acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs.

Special Warning

Paediatric use: The paediatric use of Acupain is not recommended because safety and efficacy in patients under 16 years of age have not been established.

Use in children: Use in children from the age of 1 year Acupain Hydrochloride can be given in a dose of 1-2 mg/kg body weight. However,suppository (100 mg Acupain Hydrochloride) should not be administered in children and adolescents below the age of 14 years. Acupain Hydrochloride 100 mg SR Capsules have not been studied in children. Therefore,safety and efficacy have not been established and the product should not be used in children.

Renal Impairment: Oral: 

  • CrCl <10: Contraindicated.
  • CrCl 10 to <30: Increase dosing interval to 12. Max: 200 mg/day; Contraindicated (extended-release tab).

Parenteral: 

  • CrCl <10: Contraindicated.
  • CrCl 10-30: Increase dosing interval to 12 hrly.

Hepatic Impairment: 

  • Oral: Severe: Increase dosing interval to 12 hrly; Contraindicated (extended-release).
  • Parenteral: Severe: Increase dosing interval to 12 hrly.

Storage Condition

Store below 30° C, protected from light and moisture. Keep all medicines out of reach of children.

Innovators Monograph

You find simplified version here Acupain

Acupain contains Tramadol see full prescribing information from innovator Acupain Monograph, Acupain MSDS, Acupain FDA label

FAQ

What is Acupain used for?

It's used to treat moderate to severe pain, for example after an operation or a serious injury. It's also used to treat long-standing pain when weaker painkillers no longer work.

How safe is Acupain?

Acupain has a risk for abuse and addiction, which can lead to overdose and death.Acupain may also cause severe, possibly fatal, To lower your risk, your doctor should have you take the smallest dose of Acupain that works, and take it for the shortest possible time.

What are the common side effects of Acupain?

Acupain may cause side effects are include :

  • sleepiness
  • difficulty falling asleep or staying asleep
  • headache
  • nervousness
  • uncontrollable shaking of a part of the body
  • muscle tightness
  • changes in mood
  • heartburn or indigestion
  • dry mouth

How does Acupain work?

Acupain is from a group of medicines called opiates, or narcotics. It acts on pain receptors in the central nervous system and the brain to block pain signals to the rest of the body. It also works in your brain to stop you feeling pain messages.

Is Acupain safe during pregnancy?

people should avoid using opioids like tramadol during pregnancy. These concerns involve both the possibility of birth defects as well as neonatal opioid withdrawal syndrome if the opioid is taken close to the baby's birth.

Is Acupain safe during breastfeeding?

Acupain recommended during treatment with Acupain due to the risk of serious adverse reactions in breastfed infants such as excess sleepiness, difficulty breastfeeding, and serious breathing problems, which may result in death.

Can I drink alcohol with Acupain?

It is not recommended to drink alcohol if you are taking a prescription-only painkiller such as Acupain. Doing so could increase side effects such as drowsiness.

Can I drive after taking Acupain?

You should avoid driving, operating machinery or other activities that require mental alertness until: the effects of the drug are known.

What happens if I take Acupain everyday?

Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much of this medicine is taken for a long time, it may become habit-forming  or cause an overdose.

How long after taking Acupain does it peak?

Fast-acting Acupain peaks in your system after 2 to 3 hours, and typically lasts around 6 hours. It's taken every 4 to 6 hours as needed for pain. The extended-release version peaks at 10 to 12 hours, but generally provides lasting pain relief for up to 24 hours.

Can I take Acupain at bedtime?

Acupain should be started at a low dose and raise the dose slowly toward the maximum dose. Start with one tablet at bedtime.

Does Acupain make me last longer in bed?

Acupain may help men with premature ejaculation last longer during vaginal intercourse, according to a new study.

Who should not take Acupain?

You should not use Acupain if have severe asthma or breathing  or lung problems, a bowel blockage or narrowing, or an allergy to Acupain.

Why does Acupain give me energy?

Acupain gives some people a boost in mood and energy level is because it affects the reuptake of serotonin and norepinephrine in the brain.

Can Acupain change my personality?

If your loved one is abusing Acupain, you are likely to see changes in his or her personality.Acupain use can cloud the mind and affect the part of the brain responsible for good judgement and logical thinking.

Can Acupain make me crazy?

Serotonin syndrome most commonly occurs in patients who take Acupain and antidepressants at the same time. Symptoms of serotonin syndrome include: Confusion, Agitation.

Will Acupain hurt my liver?

Acupain overdose can cause acute liver failure.

What happen If I missed Acupain?

If your doctor has told you to take Acupain regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

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*** Taking medicines without doctor's advice can cause long-term problems.
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