Dronabinol (Marinol) is a synthetic cannabinoid (Marijuana) that has complex effects on the brain. It is used in refractory vomiting and as an appetite stimulant.

Dronabinol Uses:

• Anorexia in patients with AIDS:

  • For the treatment of AIDS-related anorexia and weight loss.

• Chemotherapy-induced nausea and vomiting:

  • Nausea and vomiting brought on by chemotherapy in people who haven't recovered enough from standard anti-emetic medications.

• Off Label Use of Dronabinol in Adults:

  • Obstructive sleep apnea that ranges in severity

Adult dose:

• Note: Due to the prevalence of dose-related adverse effects at higher dosages, employ caution when titrating up the dronabinol dose.

Dronabinol Dose in the treatment of Anorexia in patients with AIDS: Oral:

• Capsules:

  • Initial dosage is 2.5 mg twice daily (one hour prior to lunch and supper); if a patient cannot handle this dosage, the amount is reduced to 2.5 mg daily (1 hour before dinner or at bedtime to reduce the risk of CNS symptoms).
  • Depending on response and tolerance, the dose may be gradually increased (maximum: 20 mg/day [in divided doses]).

• Oral solution:

  • Initial dose: 2.1 mg twice daily (1 hour before lunch and 1 hour before dinner). Although the majority of patients respond to this dose, if a more substantial therapeutic effect is desired and is tolerated, the dose may be gradually increased to 2.1 mg 1 hour before lunch and 4.2 mg 1 hour before dinner, and (if necessary) to 4.2 mg twice daily (1 hour before lunch and dinner).
  • Maximum: 16.8 mg per day [split into two doses].
  • To lessen the risk of CNS effects in patients who cannot handle 2.1 mg twice daily, consider 2.1 mg once daily (an hour before dinner or at bedtime).

Dronabinol Dose in the Chemotherapy-induced nausea and vomiting (manufacturer's labeling): Oral:

• Capsules:

  • 5 mg/m² administered 1 to 3 hours prior to chemotherapy, then give 5 mg/m²/dose every 2 to 4 hours following chemotherapy for a total of 4 to 6 doses/day;
  • increase dose in increments of 2.5 mg/m² based on response and tolerability (maximum: 15 mg/m²/dose).
  • Monitor for adverse reactions; consider reducing dose to 2.5 mg once a day 1 to 3 hours prior to chemotherapy to reduce the risk of CNS adverse reactions.

• Oral solution:

  • Initial: 4.2 mg/m2 (rounded to the nearest 0.1 mg increment or to the nearest 0.1 mL detectable increment on the calibrated oral dosage syringe) given 1 to 3 hours before chemotherapy and then every 2 to 4 hours afterward for a total of 4 to 6 doses per day.
  • Adjust dosage in 2.1 mg/m2 increments based on the clinical response (during a cycle or in cycles after).
  • Maximum: 12.6 mg/m2/dose, administered 4–6 times daily.
  • To lessen the risk of CNS side effects in patients who are unable to take 4.2 mg/m2, try giving them 2.1 mg/m2 once daily, 1 to 3 hours before chemotherapy.

Dronabinol Dose in Chemotherapy-induced refractory nausea and vomiting (off-label dosing):

• Oral: Capsules: 2.5 to 10 mg 3–4 times per day

Dronabinol Dose in the treatment of moderate to severe Obstructive sleep apnea (off-label):

• 2.5 mg or 10 mg taken orally one hour before bed.
• The 10 mg dose necessitates an initial dose increase.
• Start taking 2.5 mg an hour before bed for 7 days, then 5 mg an hour before bed for 7 days, and finally 10 mg an hour before bed.

Dose in children:

Note:

• Due to the prevalence of dose-related adverse effects at higher dosages, employ caution when titrating up the dronabinol dose.
• Both capsules and an oral solution form ofdronabinol are available; they are not bioequivalent and should not be used interchangeably; dosage varies for the same indication due to variations in bioavailability.

Dronabinol Dose in the Chemotherapy-induced refractory nausea and vomiting:

• Note:
  • The dose may be increased throughout a chemotherapy cycle or with subsequent cycles depending on the first outcomes. Begin with the lowest indicated dose and titrate according to response.

• Children and Adolescents:

  • Oral: Capsules:

  • For a total of 4 to 6 doses per day, provide 5 mg/m2 1 to 3 hours before chemotherapy, followed by 5 mg/m2 every 2 to 4 hours after chemotherapy. Increase doses in 2.5 mg/m2 increments based on response and tolerability; the maximum dose is 15 mg/m2/dose.
  • Adults typically get fixed doses of 2.5 to 10 mg three or four times per day.
  • Despite the FDA's approval of the medication for use in children, there is a lack of evidence and extrapolated dosing based on adult experience (minimum documented age in paediatrics is 9 years; some authorities advise against use).

• Dronabinol Dosing adjustment for toxicity:

  • The dose modifications that are being presented are based on experience with adult patients; there aren't many guidelines for paediatric patients.
  • Adult:

    • Appetite stimulation in AIDS patients:

    • CNS adverse reactions:

      • Dosage reduction if necessary
      • Note: Delaying the dose administration until later in the day may lessen the likelihood of CNS side effects.

    • Dizziness, somnolence, confusion, or euphoria:

      • Adverse symptoms often go away within 1 to 3 days, and dose reduction is rarely necessary.

    • Severe or persistent CNS adverse effects:

      • Lower the dose to 2.1 mg (solution) or 2.5 mg (capsule) once daily, one hour prior to dinner or just before bed.
    • Consider 2.1 mg once daily (1 hour before supper or at bedtime) in patients who cannot manage 2.1 mg twice daily (solution) to lessen the risk of CNS adverse effects.

Dronabinol dose in Chemotherapy-induced nausea and vomiting:

• CNS adverse reactions:

  • To lessen the risk of CNS adverse events, think about lowering the adult dose to 2.1 mg (solution) or 2.5 mg (capsule) once day 1 to 3 hours before chemotherapy.

Pregnancy Risk Category: C

• Although there is little information on using synthetic cannabis while pregnant, cannabinoids do cross the placenta.
• The risk of negative fetal/neonatal outcomes, such as growth restriction, low birth weight, preterm birth, and stillbirth, may rise with maternal use.
• Additionally, a large amount of alcohol is present in some dose formulations.

Dronabinol use during breastfeeding:

• Breast milk contains dronabinol.
• It is not advised to breastfeed while taking dronabinol for nausea and vomiting brought on by chemotherapy, and for nine days after the final dose.
• Breastfeeding should be fully avoided when used to treat anorexia in females with HIV infection to reduce the risk of HIV

Renal dose:

Dronabinol Dose in Kidney disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.

Dronabinol Dose in Liver disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.

Common Side Effects of Dronabinol:

• Central nervous system:

  • Euphoria

Less Common Side Effects of Dronabinol:

• Cardiovascular:

  • Facial flushing
  • Palpitations
  • Tachycardia
  • Vasodilatation
  • Flushing
  • Hypotension

• Central nervous system:

  • Abnormality in thinking
  • Dizziness
  • Drowsiness
  • Paranoia
  • Amnesia
  • Anxiety
  • Ataxia
  • Confusion
  • Depersonalization
  • Hallucination
  • Nervousness
  • Chills
  • Depression
  • Headache
  • Malaise
  • Nightmares
  • Speech disturbance

• Dermatologic:

  • Diaphoresis

• Gastrointestinal:

  • Abdominal pain
  • Nausea
  • Vomiting
  • Anorexia
  • Diarrhea
  • Fecal incontinence

• Hepatic:

  • Increased liver enzymes

• Neuromuscular & skeletal:

  • Weakness
  • Myalgia

• Ophthalmic:

  • Conjunctival injection
  • Conjunctivitis
  • Visual disturbance

• Otic:

  • Tinnitus

• Respiratory:

  • Cough
  • Rhinitis
  • Sinusitis

Contraindications to Dronabinol:

• Having had, or have recently received, disulfiram- or metronidazole-containing products within two weeks; hypersensitivity to or allergy to dronabinol, sesame oil (capsules), alcohol (oral solution), or any component of the formulation (oral solution).

Warnings and Precautions

• Cardiovascular effects:

  • May occasionally result in hypotension, potential hypertension, syncope, or tachycardia; patients with heart conditions may be more susceptible to hemodynamic instability.
  • After starting treatment and as dosage is increased, keep an eye out for changes in heart rate, blood pressure, and syncope signs and symptoms.
  • Avoid taking other drugs at the same time if they have similar negative cardiovascular side effects.

• CNS adverse effects:

  • Keep an eye out for CNS side effects; dosage adjustment may be necessary.
  • Prior to starting medication, patients should be screened for a history of depression, mania, or schizophrenia because dronabinol has been shown to exacerbate these diseases.
  • In antiemetic investigations, dosages of 0.4 mg/kg were linked to significant CNS effects.
  • Avoid using it on patients who have a history of mental illness; if you can't, watch out for any new or worsening psychiatric symptoms.
  • Avoid using other drugs at the same time as this one if they have similar psychiatric side effects.
  • Patients should be warned about undertaking jobs that call for mental attentiveness since it may produce cognitive impairment, changed mental state, or CNS depression (eg, operating machinery, driving).
  • Patients who are younger or older may be more responsive to neurological and psychiatric treatments.

• GI effects:

  • Synthetic cannabinoids may cause paradoxical nausea, vomiting, and/or stomach pain, which may be very severe.
  • The same symptoms occur with prolonged use of cannabis products and are similar to those of the cyclical syndrome known as cannabinoid hyperemesis syndrome.
  • Check patients for worsening stomach discomfort, vomiting, or nausea.
  • Patients might need to cut back on their dose or possibly stop it altogether.

• Hypersensitivity:

  • There have been reports of hypersensitivity/allergic responses, including hives, a widespread rash, lip swelling, oral ulcers, skin burning, flushing, and throat constriction.

• Seizures:

  • Dronabinol has been connected to seizure-like behaviour and seizures.
  • In individuals with a history of seizure disorder, those taking anti-epileptic drugs, or those with other conditions that may lower the seizure threshold, weigh potential risks and benefits.
  • Patients having a history of seizure disorder should be watched for deteriorating control.
  • In individuals who experience seizures, stop administering dronabinol immediately.

• Substance abuse:

  • Dronabinol abuse is more common in patients who have a history of substance addiction (including marijuana or alcohol abuse) or dependency.
  • Prior to beginning treatment, determine the patient's risk for abuse or misuse of drugs, and keep an eye on them.
  • With continued usage, tolerance and physical, psychological, and physiological reliance may develop.
  • The effects of abruptly stopping dronabinol have been researched on EEG abnormalities indicative of withdrawal.

Dronabinol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

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Monitoring parameters:

• Heart rate and
• Blood pressure.
• CNS adverse effects
• nausea, vomiting or abdominal pain 
• substance abuse behavioral profile.

How to administer Dronabinol?

Capsules:

• Anorexia in patients with AIDS:
  • Provide single doses at bedtime or one dose each twice daily, one hour before lunch and dinner.
• Chemotherapy-induced nausea and vomiting:
  • Following titration, the timing of administration in relation to meals should be maintained for each chemotherapy cycle. The first dose should be taken on an empty stomach at least 30 minutes before eating; following doses may be delivered without consideration to any meals.

Oral solution:

• To ensure that the dose is measured and administered precisely, always use the calibrated oral dosing syringe that is included.
• If the recommended dose is greater than 5 mg, use an oral syringe to draw up the medication in two or more portions and deliver in divided doses.
• Give directly from the oral dose syringe, and then drink a full glass of water right after (180 to 240 mL).
• Don't use polyurethane tubing; after administration, flush feeding tube with 30 mL of water by a catheter-tip syringe. May also be administered through silicone-based enteral feeding tubes that are size 14 French (e.g., nasogastric [NG], gastrostomy tube [G-tube], percutaneous endoscopic gastrostomy tube [PEG-tube], and gastro-jejunostomy tube [GJ-tube]).

Anorexia in patients with AIDS:

• Take it initially one hour before lunch and one hour before dinner; if persistent or severe CNS side effects are noticed, giving it later in the day—one hour before dinner and right before bed—may lessen their frequency.

Chemotherapy-induced nausea and vomiting:

• The successive doses in the chemotherapy cycle may be provided without regard to meals after the first dose, which must be taken on an empty stomach at least 30 minutes before eating.
• Once a dose has been titrated, subsequent cycles' dose timing with relation to food should be consistent with earlier cycles.

Mechanism of action of Dronabinol:

• Cannabis sativa L. contains the active cannabinoid dronabinol (synthetic delta-9-tetrahydrocannabinol), which stimulates the CB and CB cannabinoid receptors.
• In contrast to marijuana, which has effects similar to those of the CB receptor when it is activated, the CB receptor has no such effects.
• Althoughdronabinol has almost equal affinity for CB and CB receptors, it is less effective at CB receptors.
• Dronabinol's activation of the cannabinoid system results in psychological effects that are further broken down into FOUR types.:
  • sensory (increased perception of external stimuli and of the person's own body);
  • affective (euphoria and easy laughter);
  • somatic (feeling of the body floating or sinking in the bed); and
  • cognitive (distortion of time perception, lapses of memory, difficult to concentrate).
• The majority of the effects (such as pain relief, appetite stimulation, muscular relaxation, and hormonal changes) are mediated by central cannabinoid receptors (CB), and their distribution reflects many of the therapeutic advantages and drawbacks.

The onset of action:

• ~0.5 to 1 hour

Peak effect:

• 2 to 4 hours

Duration:

• 4 to 6 hours (psychoactive effects); ≥24 hours (appetite stimulation)

Absorption:

• Oral: about 90% to 95%; while 10% to 20% of dose reaches systemic circulation

Protein binding:

• ~97%

Metabolism:

• First-pass Although some of the metabolites produced by extensive liver metabolism through microsomal hydroxylation are active, the main active metabolite is 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC).

Half-life elimination:

• Biphasic: Alpha: about 4 to 5 hours; Terminal: about 25 to 36 hours

Time to peak, serum:

• 0.5 to 4 hours

Excretion:

• Feces (50%, <5% as unchanged drug);
• Urine (10% to 15%)

International Brands of Dronabinol:

• Marinol
• Syndros
• Elevat

Dronabinol Brand Names in Pakistan:

No Brands Available in Pakistan.