Carlosafine

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

Carlosafine exerts its analgesic effect via high affinity binding to the μ-opioid receptors in the CNS. It displays partial μ-opioid agonist activity and weak kappa antagonist activity.

Carlosafine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Carlosafine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Dependence

Carlosafine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Carlosafine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion.

Trade Name Carlosafine
Availability Prescription only
Generic Buprenorphine
Buprenorphine Other Names Buprenophine, Buprenorfina, Buprenorphine, Buprenorphinum
Related Drugs Subutex, Sublocade, Zubsolv, Probuphine, Buprenex, Bunavail, Vivitrol, aspirin, acetaminophen, tramadol
Type
Formula C29H41NO4
Weight Average: 467.6401
Monoisotopic: 467.303558805
Protein binding

Buprenorphine is approximately 96% protein-bound, primarily to alpha- and beta-globulin.

Groups Approved, Illicit, Investigational, Vet approved
Therapeutic Class Opioid analgesics
Manufacturer Glenmark Pharmaceuticals Europe Ltd
Available Country United Kingdom
Last Updated: September 19, 2023 at 7:00 am
Carlosafine
Carlosafine

Uses

Carlosafine is used for Moderate to severe pain, Anaesth premed, Opioid dependence, Anaesth premed, Perioperative analgesia

Carlosafine is also used to associated treatment for these conditions: Opioid Dependence, Severe Pain, Moderate Pain

How Carlosafine works

Carlosafine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. It demonstrates a high affinity for the mu-opioid receptor but has lower intrinsic activity compared to other full mu-opioid agonists such as heroin, oxycodone, or methadone. This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the "ceiling effect" where once a certain dose is reached buprenorphine's effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around 32mg, resulting in a lower risk of overdose compared to methadone and other full agonist opioids. It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours.

Carlosafine's high affinity, but low intrinsic activity for the mu-opioid receptor also means that if it is started in opioid-dependent individuals, it will displace the other opioids without creating an equal opioid effect and cause a phenomenon known as "precipitated withdrawal" which is characterized by a rapid and intense onset of withdrawal symptoms (i.e. anxiety, restlessness, gastrointestinal distress, diaphoresis, intense drug cravings, and tachycardia). Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.

Carlosafine is commercially available as the brand name product Suboxone which is formulated in a 4:1 fixed-dose combination product along with naloxone, a non-selective competitive opioid receptor antagonist. Combination of an opioid agonist with an opioid antagonist may seem counterintuitive, however this combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously.

Dosage

Carlosafine dosage

Adult:

  • Oral: Sublingual Moderate to severe pain: 200-400 mcg 6-8 hourly.
  • IV: Perioperative analgesia: 300-450 mcg via slow inj.
  • IV/IM: Moderate to severe pain: 300-600 meg 6-8 hourly.
  • IM: Anesthesia premed: 300 meg.

Severe hepatic Impairment: Dose adjustment needed.

Side Effects

Common side effects are CNS depression, including somnolence, dizziness, alterations in judgment and levels of consciousness, including coma; sedation, dizziness, sweating, vertigo, headache; nausea, vomiting, dry mouth, constipation, dyspepsia, abdominal cramps, flatulence, diaphoresis; rash, urticaria, pruritus; miosis, blurred vision, hallucinations and other psychotomimetic effects; hypotension leading to syncope, HTN, tachycardia, bradycardia, ECG abnormalities.

Toxicity

Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death.

Precaution

Patient with pulmonary impairment or compromised respiratory iratory function (e.g. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, pre-existing respiratory depression). Patient with hypothyroidism, myxedema, adrenocortical insufficiency (e.g. Addison's disease), dysfunction of biliary tract including acute pancreatitis, acute alcoholism, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy or urethral stricture; comatose patients. Patient with CNS depression, history of seizure disorders, head injury, intracranial lesions or conditions in which intracranial pressure may be increased. Patient with personal or family history of QT interval prolongation, hypokalaemia or unstable cardiac disease (e.g. AF, CHF, myocardial ischaemia), particularly in transdermal admin. Hepatic or renal impairment. Pregnancy and lactation.

Interaction

Plasma-buprenorphine concentrations may be affected when co-administered with drugs that induce or inhibit CYP3A4 isoenzyme. Enhanced depressant effects of other CNS depressants, other opiate agonists, anaesth, antihistamines, muscle relaxants, tranquilisers (e.g. phenothiazines), sedatives and hypnotics (e.g. benzodiazepines). Increased and/or prolonged activity with drugs that may reduce hepatic blood flow (e.g. halothane). Receiving class IA (e.g. quinidine, procainamide) or class III (e.g. sotalol, amiodarone) antiarrhythmic agents with transdermal buprenorphine may increase the risk of QT interval prolongation.

Food Interaction

  • Avoid alcohol. Ingesting alcohol may increase the sedative and CNS depressant effects of buprenorphine.
  • Avoid grapefruit products. Grapefruit inhibits the metabolism of buprenorphine through CYP3A4, which increases the serum levels buprenorphine.
  • Take separate from meals. When buprenorphine is formulated as a sublingual tablet or buccal film, avoid eating or drinking until the dosage form is completely dissolved.

Carlosafine Alcohol interaction

[Major] GENERALLY AVOID:

Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death.

Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection.

The mechanism of interaction probably involves some degree of additive pharmacologic effects.

Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists.

Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.



The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate.

If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect.

Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol.

Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction.

For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms.

Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

Volume of Distribution

Carlosafine is highly lipophilic, and therefore extensively distributed, with rapid penetration through the blood-brain barrier. The estimated volume of distribution is 188 - 335 L when given intravenously. It is able to cross into the placenta and breast milk.

Elimination Route

Bioavailablity of buprenorphine/naloxone is very high following intravenous or subcutaneous administration, lower by the sublingual or buccal route, and very low when administered by the oral route. It is therefore provided as a sublingual tablet that is absorbed from the oral mucosa directly into systemic circulation.

Clinical pharmacokinetic studies found that there was wide inter-patient variability in the sublingual absorption of buprenorphine and naloxone, but within subjects the variability was low. Both Cmax and AUC of buprenorphine increased in a linear fashion with the increase in dose (in the range of 4 to 16 mg), although the increase was not directly dose-proportional. Carlosafine combination with naloxone (2mg/0.5mg) provided in sublingual tablets demonstrated a Cmax of 0.780 ng/mL with a Tmax of 1.50 hr and AUC of 7.651 ng.hr/mL.

Coadministration with naloxone does not effect the pharmacokinetics of buprenorphine.

Half Life

Carlosafine demonstrates slow dissociation kinetics (~166 min), which contributes to its long duration of action and allows for once-daily or even every-second-day dosing. In clinical trial studies, the half-life of sublingually administered buprenorphine/naloxone 2mg/0.5mg was found to be 30.75 hours.

Clearance

Clearance may be higher in children than in adults. Plasma clearance rate, IV administration, anaesthetized patients = 901.2 ± 39.7 mL/min; Plasma clearance rate, IV administration, healthy subjects = 1042 - 1280 mL/min.

Elimination Route

Carlosafine, like morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. It is primarily eliminated via feces (as free forms of buprenorphine and norbuprenorphine) while 10 - 30% of the dose is excreted in urine (as conjugated forms of buprenorphine and norbuprenorphine).

The overall mean elimination half-life of buprenorphine in plasma ranges from 31 to 42 hours, although the levels are very low 10 hours after dosing (majority of AUC of buprenorphine is captured within 10 hours), indicating that the effective half-life may be shorter.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (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 foetus.

Contraindication

Transdermal: Patient with known or suspected paralytic ileus, substantial respiratory depression or severe bronchial asthma. Management of acute, intermittent, mild, or short-term (including post-op) pain. Concomitant admin of IV buprenorphine and oral diazepam. Concurrent use or w/in 14 days of discontinuation of MAOIs.

Acute Overdose

Symptoms: Resp depression, sedation, somnolence, nausea, vomiting, CV collapse and marked miosis.

Management: Supportive treatment. May use naloxone or resp stimulants if appropriate.

Storage Condition

Store between 15-30° C. Protect from prolonged exposure to light. Avoid freezing.

Innovators Monograph

You find simplified version here Carlosafine

Carlosafine contains Buprenorphine see full prescribing information from innovator Carlosafine Monograph, Carlosafine MSDS, Carlosafine FDA label

FAQ

What is Carlosafine used for?

Carlosafine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue, in the cheek, by injection, as a skin patch, or as an implant.

How safe is Carlosafine?

When taken as prescribed, Carlosafine is safe and effective. Carlosafine has unique pharmacological properties that help: Diminish the effects of physical dependency to opioids, such as withdrawal symptoms and cravings. Increase safety in cases of overdose.

How does Carlosafine work?

Carlosafine works by changing the way the brain and nervous system respond to pain.

What are the common side effects of Carlosafine?

Common side effects may include:

  • dizziness, drowsiness, blurred vision, feeling drunk, trouble concentrating;
  • withdrawal symptoms;
  • tongue pain, redness or numbness inside your mouth;
  • nausea, vomiting, constipation;
  • headache, back pain;
  • fast or pounding heartbeats, increased sweating; or.
  • sleep problems (insomnia).

Is Carlosafine safe during pregnancy?

Carlosafine is a widely used opioid medication considered safe for women during pregnancy.

Is Carlosafine safe during breastfeeding?

Because of the low levels of Carlosafine in breastmilk, its poor oral bioavailability in infants, and the low drug concentrations found in the serum and urine of breastfed infants, its use is acceptable in nursing mothers.

When should Carlosafine be administered?

Carlosafine should be taken at least six hours after the last dose of heroin.

How should I take Carlosafine?

Place the medication under your tongue for 5 to 10 minutes and let it dissolve completely. If you are prescribed more than one tablet each day, you may place all of the tablets under your tongue at once or place two tablets at a time under your tongue. Do not swallow or chew this medication.

Can I drink water after taking Carlosafine?

You should avoid drinking, eating, or smoking 15 minutes before and after the dose and until it dissolves.

How many time can I take Carlosafine daily?

Use this medication as directed by your doctor, usually once daily. Place the medication under your tongue for 5 to 10 minutes and let it dissolve completely.

How much Carlosafine can I take daily?

The recommended target dosage of Carlosafine is 16 mg as a single daily dose.

How long does Carlosafine take to work?

Fast-acting Carlosafine tablets take around 1 to 2 hours to work. Carlosafine patches can take up to a day or two to start working but they will last longer. Patches are usually given after Carlosafine tablets. This is to make sure that you have pain relief from the tablets until the patches start to work.

What is the half life of Carlosafine?

Carlosafine has a long half-life of 24 to 42 hours.

Can Carlosafine be used long-term?

For treatment professionals and treatment systems: Both methadone and Carlosafine are helpful medications for reducing illicit opioid use over the long-term (i.e., several years).

How long can I take Carlosafine?

You are much less likely to relapse if you taper off Carlosafine gradually once your life becomes more stable, and you haven't used non- prescribed opioids for at least six months.

Does Carlosafine cause weight gain?

Weight gain or weight loss are not side effects that have been reported in studies of Carlosafine.

Can Carlosafine cause depression?

Research also shows that while Carlosafine-naloxone causes a significant decline in depression severity during treatment, if discontinued suddenly, there is a significant increase in depressive levels.

Who should not take Carlosafine?

You should not use Carlosafine if you are allergic to Carlosafine. To make sure Carlosafine is safe for you, tell your doctor if you have ever had: breathing problems, sleep apnea; enlarged prostate, urination problems; liver or kidney disease; abnormal curvature of the spine that affects breathing; problems with your gallbladder, adrenal gland, or thyroid; a head injury, brain tumor, or seizures; or alcoholism or drug addiction.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line. An opioid overdose can be fatal, especially in a child or other person using the medicine without a prescription. Overdose symptoms may include severe drowsiness, pinpoint pupils, slow breathing, or no breathing.

What happen If I missed Carlosafine?

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Will Carlosafine affect my fertility?

Carlosafine does not affect fertility or your ability to become pregnant if you are a female or to make someone else pregnant if you are a male.

Does Carlosafine affect heart rate?

Carlosafine has been reported to cause a decrease in heart rate, systolic and diastolic blood pressure, and stroke volume in anaesthetized dogs.

Is Carlosafine bad for my kidneys?

Carlosafine, as well as other opioids, can also affect the functioning of the kidneys. Because Carlosafine affects the water retained in the kidneys, a person may have to use the bathroom more frequently than they had before.

Can Carlosafine affects my liver?

Therapy with Carlosafine is associated with mild and transient serum enzyme elevations, and with moderate-to-severe clinically apparent liver injury when abused by intravenous administration or the sublingual formations.

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