Dronabinol with cannabidiol oromucosal
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oromucosal formulation of Cannabis sativa extracts dronabinol with cannabidiol.
Multiple sclerosis - moderate to severe spasticity: adjunctive treatment
It may take up to 2 weeks to find the optimal dose. Undesirable effects may occur during this time. These are usually mild and resolve in a few days. However, depending on the seriousness and intensity of these reactions, consider maintaining the dose, reducing the dose or interrupting treatment.
The patient's response to treatment should be reviewed after 4 weeks. If a significant improvement in spasticity related symptoms is not seen during this initial trial of therapy, treatment should be stopped.
The long term treatment should be re-evaluated periodically.
A titration period is required to reach optimal dose. The number and timing of sprays will vary between patients.
The number of sprays should be increased each day following the pattern below:
1 spray in the evening.
1 spray in the evening.
2 sprays in the evening.
2 sprays in the evening.
1 spray in the morning, 2 sprays in the evening.
1 spray in the morning, 3 sprays in the evening.
1 spray in the morning, 4 sprays in the evening.
2 sprays in the morning, 4 sprays in the evening.
2 sprays in the morning, 5 sprays in the evening.
3 sprays in the morning, 5 sprays in the evening.
3 sprays in the morning, 6 sprays in the evening.
4 sprays in the morning, 6 sprays in the evening.
4 sprays in the morning, 7 sprays in the evening.
5 sprays in the morning, 7 sprays in the evening.
The morning dose can be taken anytime between waking and midday. The evening dose can be taken anytime between 4pm and bedtime. There should be at least a 15 minute gap between sprays.
The patient may continue to gradually increase the dose by one spray per day, up to a maximum of 12 sprays per day, until they achieve optimum symptom relief.
Following the titration period, patients are advised to maintain the optimum dose achieved. The average dose in clinical trials for patients with multiple sclerosis is 8 sprays per day. Once the optimum dose has been achieved, patients may spread the doses throughout the day according to individual response and tolerability.
Dose adjustments may be appropriate if there are any changes in the severity of the patient's condition, changes to their concomitant medication, or if troublesome adverse reactions develop.
Doses greater than 12 sprays per day are not recommended.
Additional Dosage Information
To minimise variability of bioavailability in the patient, administration of dronabinol and cannabidiol should be standardised as far as possible in relation to food intake.
Children under 18 years
History of psychiatric disorder
Severe cardiovascular disorder
Precautions and Warnings
Females of childbearing potential
History of drug misuse
Severe hepatic impairment
Severe renal impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Treatment to be initiated and supervised by a specialist
Vary application site on oromucosal surface with each use
Inspect oral mucosa regularly in patients on long term treatment
Monitor and discontinue if appropriate if psychiatric or CNS problems occur
Interrupt treatment if oral mucosal lesions occur
Therapy should be stopped if there is no benefit after 4 weeks treatment
Advise patient to moderate alcohol intake during treatment
Female:Barrier contraception required during & for 3 months after treatment
Male & female: Contraception required during & for 3 months after treatment
Advise patient of increased risk of falls
Elderly patients may be more prone to develop some CNS adverse reactions and should take extra care in terms of personal safety such as preparation of hot food and drinks.
A thorough evaluation of the severity of spasticity related symptoms and of the response to standard anti-spasticity medication should be performed prior to the initiation of treatment.
There is a risk of an increase in incidence of falls in patients whose spasticity has been reduced and whose muscle strength is insufficient to maintain posture or gait. In addition, CNS adverse reactions could potentially have an impact on various aspects of personal safety, such as with food and hot drink preparation.
Patients be advised that if they travel to another country it may not be legal for them to take this medicine into some countries. They should be encouraged to check the legal status before travelling with dronabinol and cannabidiol.
Patients who observe discomfort or ulceration at the site of application are advised to vary the site of application within the mouth and should not continue spraying onto sore or inflamed mucous membrane. Regular inspection of the oral mucosa is also advised in long term administration. If lesions or persistent soreness are observed, medication should be interrupted until complete resolution occurs.
Pregnancy and Lactation
Contraindicated during pregnancy.
Pregnant women should avoid using the product in all circumstances. If it has been used, this does not justify interruption of the pregnancy, and neither does sporadic use justify any additional diagnostic procedures (Schaefer, 2007).
Men and women of childbearing potential should use barrier contraception for the duration of therapy and for three months after discontinuation of therapy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Contraindicated during breastfeeding.
Tetrahydrocannabinol is found in breast milk. It is rapidly distributed into the brain and fat, where it is stored. The half-life is up to 57 hours, and oral absorption is 100% (Schaefer, 2007).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving. When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them. It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1.The medicine has been prescribed to treat a medical or dental problem and 2.The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine and 3.The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk
Advise patient that the spray should be directed at various sites on the oromucosal surface, changing the application site for each use of the product to minimise risk of local adverse reactions.
Advise patient to moderate alcohol intake whilst on this medication.
Advise men and women of child bearing potential to ensure adequate contraception during treatment and for 3 months after withdrawal of therapy.
Advise patients using hormonal contraceptives to use an additional barrier method contraceptive during treatment and for 3 months after withdrawal of therapy.
Advise patient that their ability to drive and operate machinery may be affected by the side effects.
Advise patients of increased risk of falls.
Changes in mood
Desquamation of the oral mucosa
Disturbances of appetite
Irritation at application site
Loss of balance
Pain at application site
Superficial tooth discolouration
Withdrawal Symptoms and Signs
The abrupt withdrawal of long-term dronabinol and cannabidiol treatment has not resulted in a consistent pattern or time-profile of withdrawal-type symptoms and the likely consequence will be limited to transient disturbances of sleep, emotion or appetite in some patients.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: April 2013
British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Summary of Product Characteristics: Sativex Oromucosal Spray. GW Pharma Ltd. Revised August 2018.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Dronabinol Last revised: March 3, 2009
Last accessed: April 8, 2013.
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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