Dronabinol (dronabinol)

The manufacturer of dronabinol oral solution states that a 4.2-mg dose of the oral solution appears to provide comparable systemic exposure to dronabinol as a 5-mg dose of the dronabinol oral capsule, under fasted conditions.

Dronabinol is administered orally as capsules (e.g., Marinol(R)) or oral solution (Syndros(R)).

When used for the management of anorexia in adults with acquired immunodeficiency syndrome (AIDS), administer dronabinol capsules and oral solution initially twice daily, 1 hour before lunch and dinner. In geriatric patients or patients unable to tolerate the recommended twice-daily dosage, administer dronabinol capsules and oral solution once daily, 1 hour before dinner or at bedtime to reduce the risk of CNS symptoms. Dosing dronabinol later in the day may help reduce the frequency of adverse CNS effects.

When used for the treatment of cancer chemotherapy-induced nausea and vomiting in adults who have failed conventional antiemetics, administer dronabinol capsules and oral solution 1-3 hours prior to chemotherapy and then every 2-4 hours after chemotherapy totaling 4-6 doses per day. In geriatric patients, consider initiating dronabinol capsules or oral solution at a lower dosage 1-3 hours prior to chemotherapy once daily to reduce the risk of CNS symptoms.

Because food delays absorption and can substantially affect systemic exposure, administer the first dose of dronabinol capsules or oral solution on an empty stomach, >=30 minutes before eating. Subsequent doses may be administered without regard to meals; however, administer dronabinol in a consistent manner relative to meals for each chemotherapy cycle once the dosage has been determined from the titration process.

When administering dronabinol oral solution, use the calibrated oral dosing syringe supplied by the manufacturer to ensure accurate measurement and administration of the drug. The oral syringe measures a maximum dose of 5 mg (i.e., 1 mL of the oral solution); if the prescribed dose is greater than 5 mg, divide the total dose into 2 or more portions and administer using the oral syringe. When preparing the oral solution, firmly insert the adapter provided by the manufacturer into the neck of the bottle before first use; the adapter should remain in place as long as the bottle is in use. A dose is dispensed by firmly inserting the oral dosing syringe tip into the adapter, and then carefully inverting the bottle and slowly withdrawing the appropriate dose into the syringe. Lastly, while the oral syringe and adaptor are connected, turn the bottle upright and remove the oral syringe from the adapter by gently pulling up. Slowly administer the dose into the back of the patient's mouth on top of the tongue. Administer a full glass of water (180-240 mL (6-8 ounces)) after each dose of dronabinol oral solution. For complete instructions on how to prepare and administer dronabinol oral solution, refer to the full prescribing information.

Dronabinol oral solution can be administered via enteral feeding tubes that are manufactured with silicone and of a size greater than or equal to 14 French, such as nasogastric, gastrostomy, percutaneous endoscopic gastrostomy, and gastro-jejunostomy tubes. Do not use with tubes manufactured of polyurethane. To prepare and administer the oral solution via feeding tube, first draw up the prescribed dose with the calibrated dosing syringe. If the prescribed dose is greater than 5 mg, divide the total dose and draw up in 2 or more portions using the oral syringe. Administer the dose via the feeding tube using the calibrated dosing syringe. Flush the feeding tube with 30 mL of water using a catheter-tip syringe. For complete instructions on how to prepare and administer dronabinol solution via a feeding tube, refer to the full prescribing information.

Store dronabinol capsules in a well-closed container in a cool environment between 8-15degreesC or alternatively in a refrigerator. Protect from freezing.

Store dronabinol oral solution in a refrigerator between 2-8degreesC (excursions permitted up to 25degreesC); the opened bottle can be stored at 25degreesC. Discard unused portion 42 days after first opening. Keep the oral solution and the oral syringe in the supplied carton.

No formal drug interaction studies have been performed with dronabinol to date. The enzyme inhibition and induction potential of dronabinol and its active metabolite have not been fully elucidated. Dronabinol is metabolized principally by cytochrome P-450 (CYP) isoenzymes 2C9 and 3A4.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Cannabinoids/Warfarin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Cannabidiol (CBD) and tetrahydrocannabinol (THC) have been shown to inhibit CYP2C9-mediated metabolism of S-warfarin in vitro.(1) Nabilone(2) and THC(1) may also displace warfarin from protein binding sites. Nabilone is an orally active synthetic cannabinoid.(2) Dronabinol is a synthetic form of THC.(3)

CLINICAL EFFECTS: Concurrent use of CBD and/or THC, dronabinol, or nabilone may result in elevated levels of warfarin and INR(1-5) and increase the risk of bleeding.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). Pharmacogenomic information: patients with a CYP2C9 intermediate metabolizer genotype, and/or 1-2 copies of a reduced function VKORC1 gene are expected to be more susceptible to this interaction. Although patients with a pre-existing CYP2C9 poor metabolizer genotype are expected to be less susceptible to effects from this drug combination, their reduced function genotypes (e.g. CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3) result in an inherently higher warfarin half-life and risk for warfarin-associated bleeding. CYP2C9 poor metabolizers generally require lower anticoagulant doses and more time (>2 to 4 weeks) to achieve effective and safe anticoagulation than patients without these CYP2C9 variants.

PATIENT MANAGEMENT: Monitor INRs frequently until stable in patients who start CBD and/or THC, dronabinol, or nabilone or have the dose adjusted.(1) A Health Canada Product InfoWatch regarding the use of cannabis and warfarin advises healthcare professionals to ask patients about their use of cannabis, particularly if patients are being treated with warfarin, due to the potential for increased INR values.(6) Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. Discontinue anticoagulation in patients with active pathologic bleeding.

DISCUSSION: In a case report, a patient who had received warfarin therapy for 11 years was hospitalized twice with bleeding episodes (gastrointestinal and nosebleeds) and elevated INRs (10.41 and 11.55) during a period of increased marijuana use. After the patient ceased marijuana use, his INRs stabilized.(4) As of September 30, 2020, Health Canada received 2 adverse reaction reports of increased INR suspected of being associated with the use of warfarin and orally ingested or sublingually administered CBD oil or CBD-dominant cannabis oil products. The first case involved a 76-year-old woman who experienced an increase in INR (4.8) less than one week after starting CBD oil. The second case was reported in an 83-year-old man who experienced an increase in INR (6.2) approximately 3 months after starting a CBD-dominant cannabis oil (1 mg/mL THC and 20 mg/mL CBD). There were no other changes to his medications. In both cases, the cannabis product was discontinued, warfarin dose was adjusted and the INR went back within therapeutic range.(6) A systematic review of one in vitro study and two case reports reviewed the interaction between warfarin and cannabis. The review noted the interaction potential of cannabis as a CYP2C9 inhibitor at clinically relevant concentrations that may inhibit warfarin metabolism.(7) In a case report, a 44-year-old male patient took warfarin 7.5 mg daily with therapeutic INRs ranging from 2 to 2.6 for at least six months. After starting CBD oil 265 mg twice daily, the patient's INR increased to 6.86. The warfarin dose was decreased by 30% and the patient's INR returned to the therapeutic range of 2-3.(8) In a case report, a 46-year-old male patient was maintained on a weekly warfarin dose of 80 mg for 5 months (INR range: 1.7 to 3.3). He started cannabidiol 5 mg/kg divided twice daily with a final daily dose titration of 20 mg/kg. Over the course of multiple weeks during the cannabidiol dose titration, an increase in INR was observed (INR increased from 3.1 before the start of cannabidiol therapy and increased to 3.4 on week two and 3.5 on week three). The warfarin weekly dose was adjusted resulting in a 20% decrease and no reported adverse bleeding events.(9) In a case report of a 35-year-old male patient on long term warfarin 10 mg daily with an INR goal of 2.5, an increase in INR to 7.2 occurred following one month of edible cannabis ingestion and cannabis smoking. The INR dropped below 4 upon discontinuation of cannabis with dose adjustments to warfarin.(10) In a case report of a 67-year-old-male patient on long term warfarin 6 mg and 7.5 mg on alternating days, an increase in INR to 5.2 occurred with using two different medical cannabis supplements. Warfarin was held for 2 days and the INR dropped to 2.8. The warfarin weekly dose was decreased by 28-29% and the patient reported no bleeding adverse events.(11) In a case report of a 85-year-old patient, use of oralmucosal medical cannabis had minimal changes in INR over a 1 year period.(12) Delta-9-tetrahydrocannabinol was found to inhibit the CYP2C9 metabolism of S-warfarin in vitro. Studies performed on polycyclic aromatic hydrocarbons found no effect of these compounds on CYP2C9, indicating that combustion may not be required for CYP2C9 inhibition.(1)

Selected Cyp2d6 Inhibitors/Metoprolol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: CYP2D6 inhibitors may inhibit the metabolism of metoprolol.(1,2)

CLINICAL EFFECTS: Concurrent use of CYP2D6 inhibitors may result in elevated levels of and toxicity from metoprolol.(1,2)

PREDISPOSING FACTORS: The interaction may be more severe in patients who are ultrarapid metabolizers of CYP2D6.(1,2)

PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy with metoprolol and inhibitors of CYP2D6. The dosage of metoprolol may need to be adjusted.(1,2)

DISCUSSION: In an open-label, randomized, cross-over study in 12 healthy males, celecoxib (200 mg BID) increased the AUC of metoprolol (50 mg) by 64%. One subject experienced a 200% increase.(3) In a randomized, double-blind, cross-over study in 7 healthy subjects, hydroxychloroquine (400 mg) increased the AUC of a single dose of metoprolol by 65%.(4) In a study in 20 Chinese patients with chronic myelogenous leukemia, imatinib (400 mg BID) increased the AUC of metoprolol (100 mg single dose) by 23%. (5) In healthy subjects, ranolazine (750 mg twice daily) increased plasma levels of a single dose of metoprolol (100 mg) by 1.8-fold.(6) CYP2D6 inhibitors include: abiraterone, asunaprevir, berotralstat, bupropion, capivasertib, celecoxib, chloroquine, cinacalcet, citalopram, clomipramine, dacomitinib, diphenhydramine, dronabinol, duloxetine, eliglustat, escitalopram, fedratinib, fluoxetine, hydroxychloroquine, imatinib, levomepromazine, lorcaserin, moclobemide, osilodrostat, paroxetine, quinine, ranitidine, ranolazine, rolapitant, and sertraline.

Selected Cyp2d6 Inhibitors/Propranolol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: CYP2D6 inhibitors may inhibit the metabolism of propranolol.(1)

CLINICAL EFFECTS: Concurrent use of CYP2D6 inhibitors may result in elevated levels of and toxicity from propranolol, including hypotension and bradycardia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy with propranolol and CYP2D6 inhibitors. The dosage of propranolol may need to be adjusted.(1)

DISCUSSION: In a pharmacokinetic study in 16 healthy volunteers, concurrent use of quinidine 200 mg (a CYP2D6 inhibitor) increased the area-under-curve (AUC) of propranolol by 2.29-fold.(2) In a pharmacokinetic study in 6 healthy subjects, concurrent use of quinidine increased propranolol AUC 2-fold.(3) A retrospective review of concurrent use of propranolol and antidepressants evaluated the risk of hospitalization or emergency room visit within 30 days of concurrent prescription. In patients receiving antidepressants with moderate to strong CYP2D6 inhibitory effects, patient were an increased risk compared to patients receiving no antidepressants (Hazard Ratio (HR) = 1.53; 95% CI 1.03-2.81 vs. HR = 1.24; 95% CI 0.82-1.88).(4) Case reports of bradycardia and cardiac adverse effects have been reported with concurrent use of propranolol and the antidepressants fluoxetine and paroxetine (strong CYP2D6 inhibitors).(5) Strong CYP2D6 inhibitors include: bupropion, dacomitinib, fluoxetine, mavorixafor, and paroxetine. Moderate CYP2D6 inhibitors include: abiraterone, asunaprevir, berotralstat, capivasertib, cinacalcet, duloxetine, eliglustat, escitalopram, levomepromazine, lorcaserin, mirabegron, moclobemide, quinine, ranolazine, and rolapitant. Weak CYP2D6 inhibitors include: desvenlafaxine, diphenhydramine, dimenhydrinate, dronabinol, fedratinib, hydroxychloroquine, imatinib, osilodrostat, ranitidine, and sertraline.(6)

Selected Weak Cyp2d6 Inhibitors/Tamoxifen

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of CYP2D6 may inhibit the conversion of tamoxifen to endoxifen (an active metabolite of tamoxifen).(1-2) The role of endoxifen in tamoxifen's efficacy has been debated and may involve a minimum concentration level.(3-5)

CLINICAL EFFECTS: Concurrent use of inhibitors of CYP2D6 may decrease the effectiveness of tamoxifen in preventing breast cancer recurrence.

PREDISPOSING FACTORS: Concurrent use of weak CYP2D6 inhibitors in patients who are CYP2D6 intermediate metabolizers should be avoided. Patients who are CYP2D6 poor metabolizers lack CYP2D6 function and are not affected by CYP2D6 inhibition.

PATIENT MANAGEMENT: Although data on this interaction are conflicting, it may be prudent to use alternatives to CYP2D6 inhibitors when possible in patients taking tamoxifen. The US manufacturer of tamoxifen states that the impact on the efficacy of tamoxifen by strong CYP2D6 inhibitors is uncertain and makes no recommendation regarding coadministration with inhibitors of CYP2D6.(12) The manufacturer of paroxetine (a strong CYP2D6 inhibitor) states that alternative agents with little or no CYP2D6 inhibition should be considered.(13) The National Comprehensive Cancer Network's breast cancer guidelines advises caution when coadministering strong CYP2D6 inhibitors with tamoxifen.(14) NCCN states when prescribing a selective serotonin reuptake inhibitor (SSRI), it is reasonable to avoid SSRIs that are strong and moderate CYP2D6 inhibitors, particularly fluoxetine and paroxetine, if an appropriate alternative exists.(14) Cancer Care Ontario breast cancer guidelines state concurrent use of weak CYP2D6 inhibitors should be closely monitored.(15) The European Society of Medical Oncology (ESMO) clinical practice guidelines for early breast cancer states patients on tamoxifen should be advised to avoid concurrent use of strong and moderate CYP2D6 inhibitors. Consider alternatives to tamoxifen if CYP2D6 inhibitors cannot be replaced with alternative agents.(16) If concurrent therapy is warranted, the risks versus benefits should be discussed with the patient.

DISCUSSION: Some studies have suggested that administration of fluoxetine, paroxetine, and quinidine with tamoxifen or a CYP2D6 poor metabolizer phenotype may result in a decrease in the formation of endoxifen (an active metabolite of tamoxifen) and a shorter time to breast cancer recurrence.(1-2,9) A retrospective study of 630 breast cancer patients found an increasing risk of breast cancer mortality with increasing durations of coadministration of tamoxifen and paroxetine. In the adjusted analysis, absolute increases of 25%, 50%, and 75% in the proportion of time of overlapping use of tamoxifen with paroxetine was associated with 24%, 54%, and 91% increase in the risk of death from breast cancer, respectively.(18) The CYP2D6 genotype of the patient may have a role in the effects of this interaction. Patients with wild-type CYP2D6 genotype may be affected to a greater extent by this interaction. Patients with a variant CYP2D6 genotype may have lower baseline levels of endoxifen and may be affected to a lesser extent by this interaction.(6-10) In a retrospective review, 1,325 patients treated with tamoxifen for breast cancer were classified as being poor 2D6 metabolizers (lacking functional CYP2D6 enzymes), intermediate metabolizers (heterozygous alleles), or extensive metabolizers (possessing 2 functional alleles). After a mean follow-up period of 6.3 years, the recurrence rates were 14.9%, 20.9%, and 29.0%, in extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively.(11) In October of 2006, the Advisory Committee Pharmaceutical Science, Clinical Pharmacology Subcommittee of the US Food and Drug Administration recommended that the US tamoxifen labeling be updated to include information about the increased risk of breast cancer recurrence in poor CYP2D6 metabolizers (either by genotype or drug interaction).(19-20) The labeling changes were never made due to ongoing uncertainty about the effects of CYP2D6 genotypes on tamoxifen efficacy. In contrast to the above information, two studies have shown no relationship between CYP2D6 genotype and breast cancer outcome.(21-23) As well, a number of studies found no association between use of CYP2D6 inhibitors and/or antidepressants in patients on tamoxifen and breast cancer recurrence,(24-28) though the studies were limited by problematic selection of CYP2D6 inhibitors and short follow-up. Weak inhibitors of CYP2D6 include: alogliptin, artesunate, celecoxib, chloroquine, cimetidine, clobazam, clomipramine, cobicistat, delavirdine, diltiazem, dimenhydrinate, diphenhydramine, dronabinol, dupilumab, echinacea, enasidenib, fedratinib, felodipine, fluvoxamine, gefitinib, hydralazine, imatinib, labetalol, lorcaserin, nicardipine, osilodrostat, ranitidine, ritonavir, sarpogrelate, sertraline, verapamil and viloxazine.(29)

Weak Cyp2d6 Inhibitors/Eliglustat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Weak inhibitors of CYP2D6 may inhibit the metabolism of eliglustat. If the patient is also taking an inhibitor of CYP3A4, eliglustat metabolism can be further inhibited.(1)

CLINICAL EFFECTS: Concurrent use of an agent that is a weak inhibitor of CYP2D6 may result in elevated levels of and clinical effects of eliglustat, including prolongation of the PR, QTc, and/or QRS intervals, which may result in life-threatening cardiac arrhythmias.(1)

PREDISPOSING FACTORS: If the patient is also taking an inhibitor of CYP3A4 and/or has hepatic impairment, eliglustat metabolism can be further inhibited.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The dosage of eliglustat with weak inhibitors of CYP2D6 in poor CYP2D6 metabolizers should be limited to 84 mg daily.(1) The dosage of eliglustat with weak inhibitors of CYP2D6 in extensive CYP2D6 metabolizers with mild (Child-Pugh Class A) hepatic impairment should be limited to 84 mg daily.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: Paroxetine (30 mg daily), a strong inhibitor of CYP2D6, increased eliglustat (84 mg BID) maximum concentration (Cmax) and area-under-curve (AUC) by 7-fold and 8.4-fold, respectively, in extensive metabolizers. Physiologically-based pharmacokinetic (PKPB) models suggested paroxetine would increase eliglustat Cmax and AUC by 2.1-fold and 2.3-fold, respectively, in intermediate metabolizers. PKPB models suggested ketoconazole may increase the Cmax and AUC of eliglustat (84 mg daily) by 4.3-fold and 6.2-fold, respectively, in poor metabolizers.(1) PKPB models suggested terbinafine, a moderate inhibitor of CYP2D6, would increase eliglustat Cmax and AUC by 3.8-fold and 4.5-fold, respectively, in extensive metabolizers and by 1.6-fold and 1.6-fold, respectively in intermediate metabolizers. PKPB models suggest that concurrent eliglustat (84 mg BID), paroxetine (a strong inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 16.7-fold and 24.2-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 7.5-fold and 9.8-fold, respectively.(1) PKPB models suggest that concurrent eliglustat (84 mg BID), terbinafine (a moderate inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 10.2-fold and 13.6-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 4.2-fold and 5-fold, respectively.(1) A single dose of rolapitant increased dextromethorphan, a CYP2D6 substrate, about 3-fold on days 8 and day 22 following administration. Dextromethorphan levels remained elevated by 2.3-fold on day 28 after single dose rolapitant. The inhibitory effects of rolapitant on CYP2D6 are expected to persist beyond 28 days.(5) Weak inhibitors of CYP2D6 include: alogliptin, artesunate, celecoxib, chloroquine, chlorpromazine, clobazam, clomipramine, desvenlafaxine, dimenhydrinate, diphenhydramine, dronabinol, dupilumab, echinacea, enasidenib, felodipine, gefitinib, hydralazine, hydroxychloroquine, lorcaserin, methadone, panobinostat, propafenone, sarpogrelate, sertraline, vemurafenib, and venlafaxine.(3,4)

*History of hypersensitivity to dronabinol or any ingredient in the formulation. Hypersensitivity reactions reported with dronabinol include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, and throat tightness.

*History of hypersensitivity to sesame oil (for dronabinol capsules (e.g., Marinol(R)) as it contains sesame oil).

*History of hypersensitivity to alcohol, or in patients who are receiving or have recently received (i.e., within 14 days) preparations containing disulfiram or metronidazole (for dronabinol oral solution (Syndros(R)) as it contains 50% dehydrated alcohol and 5.5% propylene glycol).

• Pregnancy

• Orthostatic hypotension

• Alcohol use disorder
• Bipolar disorder
• Depression
• Drug abuse
• Hypertension
• Hypotension
• Lower seizure threshold
• Schizophrenia
• Seizure disorder
• Tachyarrhythmia

The most common adverse reactions (>=3%) are abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, abnormal thinking, and vomiting.

More Frequent

• Acute cognitive impairment
• Hallucinations
• Mood changes

Less Frequent

• Memory impairment
• Palpitations
• Tachycardia
• Vasodilation of blood vessels

Rare or Very Rare

• Abnormal hepatic function tests
• Accidental fall
• Conjunctivitis
• Depersonalization
• Depression
• Drug-induced psychosis
• Dysarthria
• Fecal incontinence
• Hypertension
• Hypotension
• Panic disorder
• Seizure disorder
• Throat constriction
• Unconsciousness

More Frequent

• Acute abdominal pain
• Concentration difficulty
• Disturbance in thinking
• Dizziness
• Drowsy
• Euphoria
• Nausea
• Paranoid disorder
• Unsteady gait
• Vomiting

Less Frequent

• Flushing
• General weakness
• Symptoms of anxiety

Rare or Very Rare

• Altered mental status
• Blurred vision
• Chills
• Cough
• Delirium
• Diarrhea
• Fatigue
• Headache disorder
• Hyperhidrosis
• Insomnia
• Involuntary muscle movement
• Lip swelling
• Malaise
• Myalgia
• Nervousness
• Nightmares
• Orthostatic hypotension
• Rhinitis
• Sinusitis
• Stinging of skin
• Syncope
• Tinnitus
• Urticaria
• Visual changes
• Xerostomia

No enhanced messaging available.

The safety and effectiveness of dronabinol have not been established in pediatric patients. Pediatric patients may be more sensitive to the neurological and psychoactive effects of the drug.

Avoid dronabinol oral solution in preterm neonates in the immediate postnatal period because of reduced metabolism of propylene glycol leading to accumulation and increased risk of possible propylene glycol-associated toxicities.

Dronabinol may cause fetal harm. Although there are limited data regarding the use of synthetic cannabinoids during pregnancy, use of cannabis during pregnancy has been associated with adverse fetal/neonatal outcomes, including fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, admission to neonatal intensive care unit, and stillbirth.

Cannabinoids (delta-9-THC) have been found in umbilical cord blood from pregnant women who reported prenatal use of cannabis (e.g., marijuana), suggesting that dronabinol may cross the placenta. In addition, dronabinol oral solution (Syndros(R)) contains alcohol, which also is associated with fetal harm (e.g., CNS abnormalities, behavioral disorders, impaired intellectual development).

In reproduction studies in mice, dronabinol (delta-9-THC) was not teratogenic; however, decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions were observed at the dosages studied, which caused maternal toxicity. Maternal administration of dronabinol in rats from implantation through weaning was associated with maternal toxicity. Prenatal exposure to delta-9-THC has resulted in neurotoxicity with adverse effects on brain development in rats, including abnormal neuronal connectivity and impairments in cognitive and motor function.

Avoid use of cannabis and dronabinol in pregnant women.

The Centers for Disease Control and Prevention recommends that mothers infected with human immunodeficiency virus (HIV) not breast-feed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission (in HIV-negative infants) and serious adverse reactions in breast-fed infants, instruct mothers not to breast-feed if they are receiving dronabinol.

For mothers with nausea and vomiting associated with cancer chemotherapy, limited data are available on the presence of dronabinol in human milk, the effects of the drug on the breast-fed infant, or its effects on milk production. The reported effects of inhaled cannabis on breast-fed infants have been inconsistent and insufficient to establish causality. Reduced bodyweight has been observed during the preweaning stage in rat offspring exposed to dronabinol in utero and during lactation. Monitor weight in breast-feeding infants of mothers with nausea and vomiting associated with chemotherapy who are receiving dronabinol capsules and in whom breast-feeding is appropriate.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for dronabinol and any potential adverse effects on the breast-fed infant from dronabinol or from the underlying maternal condition.

In geriatric patients, exercise caution in dosage selection of dronabinol, usually starting at the low end of the recommended dosage range because these patients have a greater frequency of falls; decreased hepatic, renal, or cardiac function; increased sensitivity to psychoactive effects; and of concomitant illnesses and medication.

For the management of anorexia in geriatric patients with AIDS with dronabinol capsules (e.g., Marinol(R)), consider an initial dosage of 2.5 mg once daily 1 hour before dinner or at bedtime to reduce the risk of CNS symptoms. For the management of cancer chemotherapy-induced nausea and vomiting in geriatric patients, consider an initial dosage of 2.5 mg/m2once daily, administered 1-3 hours before chemotherapy to reduce the risk of CNS symptoms.

For the management of anorexia in geriatric patients with AIDS with dronabinol oral solution (Syndros(R)), consider an initial dosage of 2.1 mg once daily 1 hour before dinner or at bedtime to reduce the risk of CNS symptoms. For the management of cancer chemotherapy-induced nausea and vomiting in geriatric patients, consider an initial dosage of 2.1 mg/m2 once daily, administered 1-3 hours before chemotherapy to reduce the risk of CNS symptoms.

Clinical studies of dronabinol capsules in patients with AIDS and cancer >=65 years of age are insufficient to determine whether they respond differently from younger patients. Elderly patients may be more sensitive to the neuropsychiatric and postural hypotensive effects of dronabinol. Elderly patients with dementia are at increased risk for falls as a result of their underlying disease state, which may be exacerbated by the CNS effects (e.g., somnolence, dizziness) associated with dronabinol. Monitor these patients closely and place them on fall precautions before starting dronabinol. In antiemetic studies, no difference in efficacy was apparent in patients >55 years of age compared to younger patients.

Dosage selection for geriatric patients should be cautious, usually starting at the lower end of the dosage range, reflecting the greater frequency of falls and of decreased hepatic, renal, and cardiac function; increased sensitivity to psychoactive effects; and concomitant illness and other drug therapy in this population.