Buvidal

What Is Buvidal?

Buvidal is an opioid drug containing buprenorphine (BUP), soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous (weekly dose only) and N-methylpyrrolidone (monthly dose only).

The active ingredient is buprenorphine.

Its main use is opioid substitution to lower heroin or morphine intake and reduce tolerance.

It is used to treat children and adolescents 16 years of age and over; use in younger people is off-label and requires professional medical consultation.

How Does Buvidal Work?

It is a partial agonist that binds to mu receptors, displacing opiates and acting as a placeholder in receptor sites.

It is a partial agonist that binds to mu receptors, displacing opiates and acting as a placeholder in receptor sites.

This incurs a ceiling effect on mu receptors; subsequent opiate administration does not increase euphoria and prevents overdose.

96mg increases the bioavailability 5.7-fold compared with lower doses of buprenorphine tablets (16mg, 24mg) [2].

Depending on the dosage, it is a sustained-release subcutaneous deposit that releases the active ingredient over a week or month.

Walsh and colleagues (2017) showed that a weekly dose of 24mg inhibited all withdrawal symptoms in the first 24 hours of administration [3].  

Weekly and monthly use results in 6.7% more cases of opiate abstinence compared with tablet variations over 24 weeks, evidencing its efficacy [1]. 

Buvidal Dosing Options

How Is Buvidal Usage Monitored?

Pain and swelling occur in 5-10% of individuals; this is monitored before every next dose.

Heroin and morphine intake is monitored via urine samples alongside medication. Treatment is stopped when these are consumed.

Observation of poor tolerance to the drug leads to lowering the dosage or trying non-buprenorphine alternatives.

Clinical assessments occur weekly/ monthly compared to daily assessments with Subutex. 

Patients can be switched between weekly or monthly injections when tolerance to the drug is observed.

Liver function tests are carried out weekly/ monthly depending on type, as use may cause hepatic injury. 

Liver function tests are carried out weekly or monthly depending on type, as use may cause hepatic injury.

How Is Reducing Buvidal Dosage Managed?

Doses are tapered slowly over months as patients acclimatise and become tolerant to new concentrations.

It is reduced from 128g to 96mg, then 64mg with three months between lowering doses [5]. 

Healthcare professionals ensure the detoxing individual has social support when usage is lowered, as this results in an increased risk for overdose.

Buvidal Compliance

How To Access Buvidal

Accessing On The NHS

GPs assess heroin/morphine addiction cases and make referrals to local community addiction teams that further assess if needed.

NHS key workers prepare treatment care plans that include either maintenance treatment or complete detox.

Where appropriate, a referral is made to residential rehab, where Buvidal is given.

Waiting for residential rehab takes up to 9 months, with a waitlist of over 6.48 million people [6].

Nurse specialists are responsible for administration in outpatient services.

Patients are monitored for side effects weekly and monthly, depending on the type used.

It is a controlled drug where take-home use is restricted; only trained healthcare professionals can administer the medication.

Accessing Through Insurance

Accessing treatment through insurance begins with a telephone consultation with the insurance provider, who will determine if the policy covers Buvidal.

Clinical assessments then take place with a medical consultant to determine whether Buvidal is needed for detox or maintenance.

When Buvidal is available through insurance, policies cover detoxification, where the cost of treatment is £3000-£4000/week.

Private residential detox starts within 3-5 days, compared to NHS waiting time of 18+ months.

Following detox, patients given buvidal can be adjusted from weekly to monthly doses; however, subsequent rehab is not covered through insurance.

Accessing Buvidal In A Rehab

Self-funded Buvidal rehab has a waitlist time of 48 hours, depending on availability for clinical assessment.

Accessing Buvidal requires personal contact with a rehab facility, where a consultant determines the need for Buvidal.

Patients are responsible for contacting rehab facilities directly compared to when claiming on insurance, where the provider is responsible.

Consultants choose Buvidal when patients have:

Consultants only administer the medication 6 hours after the patient last used heroin or 24 hours after the patient has last used Dolophine.

Illicit drug use during Buvidal rehabilitation requires re-titration of doses to ensure efficacy.

Detox lasts for 7 days, while patients are kept in rehab for 28+ days for therapeutic intervention and observation.

Accessing Buvidal When Transitioning From Primary To Secondary Care

Secondary care practices do not prescribe Buvidal, but visiting nurse specialists inject individuals as part of a follow-up treatment care plan.

Poor social support and inadequate housing disallow full addiction recovery, so Buvidal is given during quasi-residential rehab to prevent relapse.

The monthly formulation prevents the need to use daily medication following detox, freeing up time for community activities to integrate back into society.

After residential rehab, staff are no longer available to remind individuals to take medication, so a long-term release formula is used in secondary care practices to avoid forgetting.

Side Effects Of Taking Buvidal

Insomnia

1mg/kg buprenorphine decreases non-rapid eye movement sleep by 22.1% and rapid eye movement sleep by 3.1%, causing insomnia in 25.2% of cases [7].

Buprenorphine reduces adenosine levels by 20%, disrupting the Pontine Recular Formation and Substantia Innominata responsible for regulating sleep, leading to insomnia [8].

Adrenal Insufficiency

5 cases of methadone-induced low cortisol (<5μg/dL) have been reported compared to 1 case for buprenorphine-type medications [9]

The treatment causes adrenal insufficiency by suppressing hypothalamic-pituitary-adrenal communication, leading to hypogonadism in up to 89% of men and  67% of women [10]

Long-term heroin/morphine use and subsequent treatment cause adrenal insufficiency, occurring in 9% to 29% of all opiate treatment use [11].

Increased/Decreased Blood Pressure

Taking BUP prolonged-release injection may lower blood pressure, leading to dizziness and light-headedness.

Feeling faint is a sign of overdose as blood pressure drops rapidly upon standing. 

Hypertension is reported in 5.1% of individuals [12].

Combining alcohol lowers blood pressure because both are central nervous system depressants.

Stopping treatment immediately causes a sudden rise in blood pressure, compared to gradually lowering dosages over time.

Serotonin Syndrome

Combining with SSRIs or MAOIs can result in serotonin syndrome. 

The active ingredient directly increases serotonin metabolites in the midbrain, leading to serotonin toxicity.

Combining buprenorphine in CAM 2038 and SSRIs causes serotonin syndrome by disinhibiting serotonin transmission in the central nervous system [13].

Skin Reactions

6.1% experience pruritus at the site of injection [14].

5.6% experience redness and swelling around the administration site [15].

17% report irritation, rash, bruising, and discolouration following treatment [16].

A 2019 study by Vorspan and colleagues demonstrated that 40% of discontinued use is due to redness and swelling at the administration site [17]. 

Who Is Most At Risk When Taking Buvidal?

Pre-Existing Respiratory Conditions

Combined use with benzodiazepines in those with pre-existing respiratory depression leads to death in severe cases.

Its use in cases of severe pre-existing breathing insufficiency leads to potentially fatal respiratory depression. 

60% of surgical procedures following opioid overdose are attributed to pre-existing Obstructive Sleep Apnoea or Cardiac Disease, making this population more at risk [18].

Combined use with alcohol is life-threatening for individuals with obstructive pulmonary disease, as both repress respiration. 

Compared with fentanyl, buprenorphine found in CAM 2038 reduces the risk of apnoea, where pre-existing breathing conditions are present [19].

(Click here for information about fentanyl rehab.)

Its maximum effect on respiratory depression ensures that higher doses do not contribute to its risk, making it a safer alternative than methadone in people with pre-existing respiratory conditions.

Pregnancy

Use during the last 3 months of pregnancy results in neonatal tremors, agitation, hypertonia, and convulsions in the newborn [20].

A case study of neonatal withdrawal syndrome peaked at day 5 postpartum with a Finnegan score of 11.1, dropping to 10.1 on day 6 [21].

One case study demonstrates a baby experiencing breathing distress due to prematurity following Mother's treatment use during pregnancy [22].

Dolophine remains the drug of choice in pregnant women due to its full risks being unknown; however, it is associated with fewer neonatal symptoms of withdrawal [23]. 

Infants ingest 1% of treatment in lactation, causing reduced milk consumption and delayed weight gain 11 days postpartum compared to babies of mothers not consuming the drug [24].

Seizures

Anti-epileptic medication gabapentinoids (gabapentin or pregabalin) with the combined use of treatment causes shallow and slow breathing, leading to a mortality rate of 7.9% [25] [26].

Gabapentin or Pregabalin with combined treatment causes drug poisoning in 31.1% compared to those who do not take gabapentinoids [27]. 

CAM 2038 is associated with increased cerebrospinal fluid pressure, causing seizures in patients with a history of intracranial lesions and head injury. 

A 2012 study by Bekjarovski and colleagues demonstrated that 2mg of buprenorphine caused generalised tonic-clonic seizure following combined tramadol and heroin use over 4 years [28].

Concurrent Medications

Combining benzodiazepines and the treatment leads to cardiovascular depression caused by slow and shallow breathing, with a mortality hazard rate of 2.05 [29] [30].

 Naltrexone and nalmefene administration during treatment causes symptoms of opiate withdrawal and blocks the therapeutic effects [31]. 

Combining Aprepitant increases exposure to the active ingredient, causing overdose if not considered in dosing.

St John's wort induces P-glycoprotein, reducing blood levels of buprenorphine and making the medication less effective.

58% of deaths related to buprenorphine are caused by the concurrent use of benzodiazepines and alcohol [32].

Alcoholics

The active ingredient is increased 3-fold in the blood of alcoholics with impaired hepatic function [33].

Intoxicated patients cannot be administered medication because informed consent cannot be given.

Acute alcoholism leads to hypersensitivity to treatment, causing slow and shallow breathing.

Alcoholics with severe kidney impairment are at risk of further damage caused by the active ingredient through mitochondrial toxicity, where 30% is excreted by the kidneys [34].

Elderly

Reduced hepatic function due to age results in increased BUP blood plasma concentrations.

Elderly patients taking this medication are more likely to have constipation and problems with urination compared to younger patients. 

Rosuvastatin used in elderly patients causes prolonged QT complexes when combined. 

The ceiling effect in the medication does not prevent fatal cardiovascular depression from occurring in the elderly, especially when patients have age-related reductions in physiological functioning [35].

Elderly patients become socially isolated with monthly treatment as visiting a clinic or pharmacy every day is no longer necessary, compared to daily supervised administration of methadone.

Mental Health Conditions 

Vs Methadone

Vs Buprenorphine

When It Is MOST Appropriate

Treatment is most appropriate when:

When It Is NOT Appropriate

It Is NOT