dronabinol

Absorption: Extensively metabolized following absorption, resulting in poor bioavailability (10–20%).

Distribution: Highly lipid-soluble. Persists in tissues for prolonged period of time.

Protein Binding: 97%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C9 isoenzyme with some metabolism by the CYP3A4 isoenzyme; the CYP2C9 isoenzyme exhibits genetic polymorphism; poor metabolizers may have significantly ↑ dronabinol concentrations and an ↑ risk of adverse effects; 50% excreted via biliary elimination. At least one metabolite is psychoactive.

Half-Life: 25–36 hr.

Time/Action Profile ⬆ ⬇

(antiemetic effect)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–4 hr	4–6 hr‡

‡Appetite stimulation lasts 24 hr or longer.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to dronabinol, marijuana, or sesame oil;
Nausea and vomiting due to any other causes;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of substance abuse;
Cardiovascular disease (due to potential adverse effects);
Mania, depression, or schizophrenia (may worsen these conditions);
History of seizures;
Patients taking sedatives, hypnotics, or other psychoactive drugs (↑ risk of adverse effects);
Pedi: Safety and effectiveness not established in children; avoid use of oral solution in preterm neonates because of ↑ risk of propylene glycol toxicity;
Geri: ↑risk of neurological, psychoactive, and cardiovascular adverse effects in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension, palpitations, syncope, tachycardia

Derm: facial flushing

EENT: dry mouth

GI: abdominal pain, nausea, vomiting

Neuro: anxiety, concentration difficulty, confusion, dizziness, drowsiness, mood change, abnormal thinking, amnesia, ataxia, depression, disorientation, euphoria, hallucinations, headache, impaired judgment, paranoia, paresthesia, SEIZURES

Misc: physical dependence, psychological dependence (high doses or prolonged therapy)

Interactions ⬆ ⬇

Drug-drug:

Additive CNS depression with alcohol, antihistamines, barbiturates, benzodiazepines, atropine, scopolamine, lithium, buspirone, muscle relaxants, opioid analgesics, tricyclic antidepressants, and sedative/hypnotics.
↑risk of tachycardia with amphetamine, atropine, scopolamine, cocaine, sympathomimetics, antihistamines, and tricyclicantidepressants.
CYP2C9 inhibitors, including amiodarone or fluconazole, may ↑ levels and risk of toxicity.
CYP3A4 inhibitors, including clarithromycin, erythromycin, itraconazole, ketoconazole, or ritonavir, may ↑ levels and risk of toxicity.
May ↑ levels and risk of toxicity of theophylline.
May ↑ protein displacement and toxicity of amphotericin B, cyclosporine, and warfarin.

Drug-Natural Products:

↑risk of tachycardia with caffeine-containing herbs (cola nut,guarana,mate,tea,coffee).
Concomitant use of kava, valerian, skullcap, chamomile, or hops can ↑ CNS depression.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

Nausea and Vomiting Associated with Cancer Chemotherapy

PO (Adults ): 5 mg/m² 1–3 hr prior to chemotherapy; may repeat every 2–4 hr after chemotherapy to a total of 4–6 doses/day. If 5 mg/m² dose is ineffective and no significant adverse reactions have occurred, dosage may be ↑ by 2.5 mg/m² to a maximum of 15 mg/m²/dose.

Anorexia Associated with Weight Loss in AIDS

PO (Adults ): 2.5 mg twice daily initially; may be gradually ↑ as needed (up to 20 mg/day). ↓ dose to 2.5 mg/day in the evening or at bedtime if unable to tolerate 5 mg/day dose.

Availability ⬆ ⬇

(Generic available)

Capsules: 2.5 mg; 5 mg; 10 mg

Assessment ⬆ ⬇

Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following the administration.
Monitor hydration, nutritional status, and intake and output. Patients with severe nausea and vomiting may require IV fluids in addition to antiemetics.
Monitor BP and HR periodically during therapy.
Monitor closely for side effects; effects of dronabinol vary with each patient. Monitor for new or worsening psychiatric symptoms, cognitive impairment, and altered mental state during therapy.
Monitor for seizure activity. Discontinue immediately if seizures develop.

Implementation ⬆ ⬇

Do not confuse dronabinol with droperidol.
Physical or psychological dependence may occur with high doses or prolonged therapy, causing a withdrawal syndrome (irritability, restlessness, insomnia, hot flashes, sweating, rhinorrhea, loose stools, hiccups, anorexia) when discontinued. This is unlikely to occur with therapeutic doses and short-term use.
PO: Store capsules in refrigerator; do not freeze.
Antiemetic: Administer 1st dose on an empty stomach >30 min before a meal. Subsequent doses can be taken without regard to meals. Keep timing of dose in relation to meal consistent for each chemotherapy cycle. May be administered prophylactically 1–3 hr before chemotherapy and repeated every 2–4 hr after chemotherapy up to 4–6 doses daily. Most patients respond to 5 mg three or four times daily.
Appetite Stimulant: Give 2.5 mg twice daily 1 hr before lunch and dinner initially. ↓ dose to 2.5 mg/day in the evening or at bedtime for patients unable to tolerate 5 mg/day dose. May ↑ dose to 2.5 mg at lunch and 5 mg before dinner or 5 mg at lunch and 5 mg after dinner if further therapeutic effect is desired and adverse effects are minimal. Most patients respond to 2.5 mg twice daily dose, but up to 10 mg twice daily have been tolerated in about 50% of patients. Adverse effects are dose related.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. Take missed doses as soon as possible but not if almost time for next dose; do not double doses. Signs of overdose (mood changes, confusion, hallucinations, depression, nervousness, fast or pounding heartbeat) may occur with increased doses.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
May cause dizziness, drowsiness, and impaired judgment and coordination. Advise patient to call for assistance when ambulating. Avoid driving or other activities requiring alertness until response to drug is known.
Instruct patient to change positions slowly to minimize orthostatic hypotension.
Advise patient to discontinue therapy and notify a health care professional immediately if seizure activity occurs.
Advise patient to notify health care professional if new or worsening mood symptoms (symptoms of mania, depression, or schizophrenia; trouble remembering things or concentrating; ↑ sleepiness; confusion; headaches; vision problems; dizziness; feeling light-headed; fainting; fast heartbeat).
Caution patient to avoid taking alcohol or other CNS depressants during therapy.
Advise patient and family to use general measures to ↓ nausea (begin with sips of liquids and small, nongreasy meals; provide oral hygiene; remove noxious stimuli from environment). Advise patient to notify health care professional if worsening nausea, vomiting, or abdominal pain occur; may require dose reduction or discontinuation of therapy.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy. Instruct patient to notify health care professional if pregnancy is planned or suspected. Advise women using therapy as an antiemetic during cancer chemotherapy to avoid breastfeeding during therapy and for 9 days after last dose. Advise HIV infected women with anorexia not to breastfeed.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇