What is the recommended use and dosage of Marinol (dronabinol)?

Marinol (Dronabinol): Recommended Use and Dosing

FDA-Approved Indications

Dronabinol is FDA-approved for two specific indications in adults: anorexia associated with weight loss in AIDS patients, and chemotherapy-induced nausea and vomiting (CINV) in patients who have failed conventional antiemetics. 1

Indication 1: AIDS-Related Anorexia and Weight Loss

Starting Dosage:

• Standard adult dose: 2.5 mg orally twice daily, one hour before lunch and dinner 1
• Elderly or intolerant patients: 2.5 mg once daily one hour before dinner or at bedtime to reduce CNS adverse effects 1
• Evening dosing reduces frequency of CNS reactions (feeling high, dizziness, confusion, somnolence) 1

Dosage Titration:

• If tolerated and additional effect needed, increase gradually to 2.5 mg before lunch and 5 mg before dinner 1
• Most patients respond to 2.5 mg twice daily 1
• May further increase to 5 mg twice daily if needed 1
• Maximum dose: 10 mg twice daily 1

Clinical Evidence:

• In AIDS patients, dronabinol increased appetite above baseline (38% vs 8% for placebo, P=0.015) and stabilized weight while placebo recipients lost 0.4 kg 2
• In a retrospective study of 117 HIV/AIDS patients who lost weight before treatment, 63% maintained or gained weight on dronabinol, with mean weight gain of 3.7 lb at 1 year 3
• Appetite loss decreased from 71% at baseline to 26% at 1 month (P<0.001) 3

Indication 2: Chemotherapy-Induced Nausea and Vomiting (Breakthrough Treatment)

Dronabinol is NOT recommended as first-line prophylaxis for CINV but rather as breakthrough treatment when optimal prophylaxis fails. 4

Starting Dosage:

• 5 mg/m² orally, administered 1-3 hours prior to chemotherapy 1
• Give every 2-4 hours after chemotherapy for total of 4-6 doses per day 1
• Elderly patients: Consider 2.5 mg/m² once daily 1-3 hours prior to chemotherapy 1
• First dose on empty stomach at least 30 minutes before eating; subsequent doses without regard to meals 1

Dosage Titration:

• May increase in 2.5 mg/m² increments based on response 1
• Maximum dose: 15 mg/m² per dose for 4-6 doses per day 1
• Psychiatric symptoms increase significantly at maximum dosage 1

Guideline-Recommended Breakthrough Dosing:

• NCCN Guidelines: 5-10 mg orally every 4-6 hours as breakthrough treatment 4
• ASCO Guidelines: Dronabinol or nabilone may be offered to patients experiencing nausea/vomiting despite optimal prophylaxis who have already received olanzapine 4
• Add one agent from a different drug class to current regimen 4

Clinical Context and Positioning

Dronabinol is positioned as a second-line or rescue agent, not first-line therapy:

For CINV Prevention (Primary Prophylaxis):

• First-line regimens include 5-HT3 antagonists, NK1 receptor antagonists, dexamethasone, and olanzapine 4
• Dronabinol is reserved for breakthrough treatment when these fail 4

For Breakthrough CINV:

• If olanzapine not used prophylactically, add olanzapine first 4
• If olanzapine already used, consider dronabinol, nabilone, or other drug classes 4
• Evidence quality for dronabinol/nabilone is intermediate 4

For Cancer-Related Anorexia:

• Insufficient evidence to recommend cannabinoids for cancer-related anorexia or taste disorders 4
• Megestrol acetate (400-800 mg/day) is preferred for appetite stimulation in cancer patients 5
• Dronabinol showed no improvement in appetite or quality of life in a 164-patient RCT of advanced cancer patients at 5 mg/day 4

Important Safety Considerations

CNS Adverse Reactions (Dose-Related):

• Common effects: feeling high, dizziness, confusion, somnolence, euphoria, thinking abnormalities 1, 2
• Usually resolve in 1-3 days without dose reduction 1
• If severe or persistent, reduce to 2.5 mg in evening or at bedtime 1
• Monitor patients and reduce dosage as needed 1

Psychiatric Risks:

• Screen for history of mania, depression, or schizophrenia before initiating 1
• Dronabinol can exacerbate these conditions 1
• Avoid use in patients with psychiatric history or monitor closely if unavoidable 1
• Cannabinoid administration in elderly may induce delirium 5

Contraindications:

• History of hypersensitivity to dronabinol or sesame oil 1
• Reported reactions include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, throat tightness 1

Drug Interactions:

• THC inhibits CYP3A4, CYP2C9, CYP2C19, potentially affecting metabolism of concurrent medications 6
• CNS effects may be additive with other CNS-active drugs 6
• Avoid high-fat meals with oral cannabis products as this significantly increases absorption 7, 6

Special Populations:

• Elderly and hepatically impaired patients at higher risk for adverse effects due to reduced clearance 7, 6
• Cardiovascular patients require close monitoring as THC affects heart rate and blood pressure 7, 6

Combination Therapy Evidence

Dronabinol plus prochlorperazine (10 mg each every 6 hours) was significantly more effective than either agent alone for CINV:

• Only 29% experienced nausea with combination vs 47% with dronabinol alone and 60% with prochlorperazine alone 8
• Prochlorperazine appeared to decrease dysphoric effects of dronabinol 8
• Vomiting occurred in 35% with combination vs 41% and 55% with single agents 8

Abuse Potential

Dronabinol has very low abuse potential:

• No evidence of abuse or diversion in clinical practice 9
• Prescription tracking shows use remains within therapeutic range 9
• No street market exists for dronabinol 9
• Slow, gradual onset; weakly reinforcing; effects generally dysphoric and unappealing 9
• Cannabis-dependent populations show no interest in dronabinol abuse 9

Medical Marijuana vs. Pharmaceutical Cannabinoids

ASCO Guidelines state evidence is insufficient to recommend medical marijuana in place of FDA-approved cannabinoids (dronabinol, nabilone) for CINV or radiation-induced nausea/vomiting 4

Key differences:

• Dronabinol and nabilone have precisely defined doses and schedules 4
• Medical marijuana preparations have variable THC/CBD content, making standardization difficult and interactions unpredictable 7, 6
• For refractory CINV in cancer patients, quality-controlled oral 1:1 THC:CBD extract may be considered 7

Patient Education Requirements

Clinicians should:

• Provide unbiased, evidence-based cannabis/THC educational resources 7
• Routinely and nonjudgmentally inquire about cannabis use 7
• Inform patients that medical marijuana remains federally Schedule I despite state legalization 7
• Educate on state and federal regulations 7
• Recommend against using cannabis/cannabinoids in place of standard medical treatments 7