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ROXANE LABORATORIES, INC. MARINOL8 (dronablnol'J II Capsules (Warning: May be habit forming) 'The USAN name for delta-9-tetrahydrocannabinol (THC). Brief Summary on Marino!' (dronabinol) Capsules. Before prescribing, see complete prescribing information. INDICATIONS AND USAGE Marino! (dronabinol) is ino,�ated for the treatment of: 1. anorexia associated with weight loss in patients with AIDS: and 2. nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. CONTRAINDICATIONS �[onabinol) is contraindicated in any patient who has , history of hypersensitivity to any cannabinoid or
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WARNINGS Marino! {dronabinol) is a medication wi1h a potential for abuse. Physicians and pharmacists should use the same care m prescribing and accounting for Marino! as they would with morphine or other drugs controlled under Schedule II (Clli of the Controlled Substances Act. Because of the nsk of diversion. it ,s recommended that prescriptions be limited to the amount necessary for the period between clinic visits. Patients receiving treatment with Marino! should be specifically warned not to drive. operate machinery. or engage m any hazardous activity until it ,s established that they are able to tolerate the drug and to pertorm such tasks safely. PRECAUTIONS General: The risk/benefit ratio of Marino! (dronabinol) use should be carefully evaluated m patients with the following medical conditions because of individual variation in response and tolerance to the etfects of Marino!. Marino! should be used with caution. in patients with cardiac disorders because of occasional hypotension. possible hypertension. syncope, or tachycardia (see CLINICAL PHARMACOLOGY). Marino! should be used with caution in patients with a history ol subslance abuse. including alcohol abuse or depen dence, because they may be more prone to abuse Marmol as well. Multiple substance abuse is common and mariJuana. which contains the same active compound, is a frequently abused substance. Marino! should be used with caution and careful psychiatric monitoring m patients with mania. depression, or schizo. phrenia because Marino! may exacerbate these illnesses. Marino! should be used with caution in patients receivmg concomitant therapy with sedatives. hypnotics or other psychoactiV1l drugs because of the potential for additive or synergistic CNS effects. Marino! should be used with caution in pregnant patients. nursing mothers. or pediatric patients because ,t has not been studied in these patient populations. Marino! should be used with caution tor treatment of anorexia and weight toss in elderly patients with AIDS because they may be more sensitive to the psychoactive effects and because its use m these patients has not been studied. Information for Patients: Patients receiving treatment with Marino! (dronabinol) should be alerted to the potential for additive central nervous system depression 1f Manno! is used concomitantly with alcohol or other CNS depressants such as benzodiarepines and barbiturates. Patients receiving treatment with Marino! should be specifically warned not to drive. operate machinery. or engage in any hazardous activity until it is established that they are able to tolerate the drug and to pertorm such tasks safely. Patients using Marmot should be advised of possible changes m mood am! other adverse behavioral effects of !he drug so as to avoid panic in the event of such manifestations. Patients should remain under the superv,s,on of a responsible adult during initial use of Marino! and following dosage adjustments. Drug Interactions: In studies involving patients with AIDS and/or cancer. Marino! (dronabinolJ has been co-admm,sternd with a va!iety of fll.edication1 (e.g., cytotoxic . agents . anti-infective agents. sedat.ives. or opioid analgesics) without resultrng m any chmcally s1gmficant drug/drug mteractmns. Although no drug/drug mteractions were discovered dunng !he clinical trials of Marino!, cannabmoids may rnteract with other medications through both metabolic and pharmacody• namic mechanisms. Dronabmol is highly protein bound to plasma proteins. and therefore. might displace other protem-
CONCOMITANT DRUG Amphetamines. cocaine, other sympathomimetic agents Atropine, scopolamine, antihistamines, other anucholinergic agents Amitriptyline. amoxapine. desipramine. other tricyclic antidepressants Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants. other CNS depressants Oisultiram Fluoxetine Antipyrine, barbiturates Theophyttine
other highly protein-bound drugs. are summarized in the following table.
CLINICAL EFFECT(Sl Additive hypertension. tachycardia. possibly can!iotoxicity Additive or super-additive tachycardia. drowsiness Additive tachycardia, hypertension. drowsiness Additive drowsiness and CNS depression
A reversible hypomanic reaction was reported m a 28 ylo man who smoked marijuana: confirmed by dechallenge and rechallenge A 21 y/o female with depression and bulimia receiving 20 mg/day lluoxe• tme X 4 wks became hypomanic after smoking manfuana: symptoms resolved aller 4 days Decreased clearance of these agents, presumably via competitive inhibiffon of metabo/lsm Increased theophylfine meta/JO/ism reported with smoking of marijuana: effect similar to that following smoking tobacco
Carcinogenesis, Mulagenesis, Impairment of fertlhty: Carcmogenic,ty studies have not been pertormed with drona• binol. .Mutagenicity testing of dronabinol was negative in an Ames test. In a tong-term study (77 days) in rats, oral admrmstralion of dronab,nol at doses of 30 to 150 mg/m2• equivalent to 0.3 to 1.5 times maximum recommended human dose (MRHD) of 90 mglm'lday in cancer patients or 2 to 10 times MRHD of 15 mglm2/day. in AIDS patients.
weight gain and number of viable pups and increased fetal mortality and early resorptions. Such effects were dose dependent and. less apparent at lower doses which produced less maternal toxicity. There are no adequate and well• controlled studies in pregnant women. Oronabrnol should be used only 1f the potential benefit justifies the potential 11sk to the fetus. Nursing Mothers: Use of Marino! is not recommended in nursing mothers smce, in addition to the secretion of HIV virus in breast milk. dronabinol is concentrated in and secreted in human breast milk and is absorbed by the nursing baby.
ADVERSE ftEACTIONI Adver!t expenenc,s 1Alormat1on s11mm1nted 1n the t�blo; btlo., .,,1 oe11,ed from well-controlled chmcal trials conducted ,n the US ,no US territories mvot,111g 474 P•t1er1t� t,poso6 tu Moffnot (dronabinol). Studies ol AIDS-related weight •osa included 1�7 oat11nf1 m••w10 dron.bir,01 .i • do'.e ct 2 S nig t•,ce oa,1y ind 67 rece1vmo placebo. Studin of different durat,or,s wer, comomed bi t0rtsi6�11110 lh• f11,1 11<1;11rr,ftce �! evtnl5 dunno the first 28 days. Sttldies ol nausn 1nd ,om1t,ng ralated tu c.11ncer th,nlQtt,er,py mtlud1111 317 p,tlent, receiving dronabinol 1Ad 68 r11:tiving placebo A c1nnabmo1d dose-related "h1or,.. �uy lauotHng flilf,011 ,,�, •1t11ghlt<Jlld ,w,,en,ss) has been reported by patients rece1V1no 1Aarmol 1n both tM ant,erne!lc {N,) and the ,.,.,�, oo,,� 1pfi,tilo M•mutanl ctrn,cal lnals (8�) (see CUNICAL TRIALS). The mo1t fraquenllyroJl)rted adver,eoxr,o11enu\111 p,1{ti11!� �ith AIO� i1t•OQ ,1,r.100-cootral!d dmical trials mvavoo the CNS and wer, reported by 3311;, of p1t1ents 1ec11,111e lillMnl Ah1101 251!\ ol p11ient, reported a minor CNS adverse event during the f,rst 2 weeks and ,bout �� rtJ10•t11d ;�r.t, ,n •••mt mil ••e� fo, t�� next 6 weeks lhereafte1. PROBAIL'l' CAUIALLl' REW£D: 1■c1,1111 trllltr IJH ,� Rates derived from clirncal tnals '" AIDS-re1ateo ,001.,,a tN+ 1�/i ""' t11tniother,py·r1,11t,d nausea {N=317). Rates were generally higher m the ent,,emelic use jg,_.• ,n p1rt11!ho•..,) ltxly as, whole: Astherna. Gartkovascutar: Palpitations. t1chyc,rd1a. v.soai1,1iw1�,1;1 llosh /Jiqesbi!i• Abdominal pa1n•. 111ose1·. •om1f1ng· 1/;Jrvous system: (Amnesiat. aAxittyMmoo�nes� (�ta.,,I). r.,1•1k,"n11 li;,jll!1s,io11,,11,M d111mtlS' , eupnona', {hallu cmat,on), par!no,d reacijon·, somnol1nc1·. tb1111l,nij lbftor<n�I • " .. · · .... ... ....... -- -----• Incidence of events 3� to 1� PROBABLY CAUSALLY RELATED: Incidence less than 1,_ Event rates derived from clinical trials m AIDS-mta1od ,11111<•,u ffi¥ Joli a,,11 ct,emome,apy 1eMeo nause. ;N�31 71. Cardiovascular: Gonjunctlvills • . hypotens,on' Digestive: Diarrhea·, fecal mcontmence. Muscu!oskelela!: Myalgias.
• Incidence of events 0.3% to 1%. CAUSAL RELATIONSHIP UNKNOWN: lacl�,m 1111 Illa■ f� The clinical significance of the mocialion of these ere11ts ;,1tt, M,,"r,11 t<1•;tJr..1tt ,,. ""'"o"'" bul they are reported as alerting information for the clinician. Bodf as , whole: Chills, headache. mela,se. fxgesff'((J: Anorexia, h1p1t1c enzyme elevation. /mprr,tory: Cough. rh1mt1s, sinusitis. SWn and Applllldages: Sweating. DRUB AIUSE AIID DEPENDENCE Marino! (dronabinol) is one of the psyct.lact1ve compound, p11,�11t "' r·,mi,t,1, ahll Js ,,bus•blt ind controlled Schedule II (GIi) und�r the ControUed Substancas Act 80th p1y,;MWQ1r11 •n4 �n,,,Mo9,t,•I dep,Mence hive been noted in healthy md1v1duals receiving dronab1nol. but addic11011 "i uw1Jmmot1 �•111 11,,,, 1111iy l)een s11en Iller prolonged high dose admm,stratmn. Chronic abuse of cannabis has been associated with dmernent; '" •tM1¥4t1,m ,t,o,,111J)11 1udg�rnrnt. and perception. The etiology of these impairments is unknown. but may be mo,,�tt•d 1'!111 u,. UHl1pir, r·•�i m of add1cllon rather thin an isolated effect ofthe drug. Ho such d1crsmen1s m psycM1og1ci1 '"'·"' or n1,""'"0i\11 ,wu1 have been associated with 1he administration of Marino! lor therapeulic purposes In an o pen-label study in patients With AIDS "'10 rtce,vld Man11ct tm o� to !f,9 »��1th,. RO ,bus•, diversion or systematic change m personality or ,ocial functioning were obw••d r.ft',p11i, 1111 ,ni:iu,.,on <J , ;ubst.ntial number of patients with a pas! history of drug abuse. An all!tnence syndrome has betn reported after the abrupt d,scooh"'•"on ,id�m,r,,..11,11 vt•u•te1•r1 A!teiv111g oosaoes of 210 mg/day for 12 to 16 consecuttve d•Yi• Within 12 hours atter a1sctmt,ou,11on o•w, -.;1,,iietrj n,,n,te,ted aymptoms such as 1rntab1t1ty, 1nsornA1.i. and restlessness. By 1pproX1mattly 2" hoot\ l'l'�I 0;11t•l>!x,I <11�i:onMu111on, witto:lraw1I symploms mtens1!ed to mctude "Mt tashes", SW!lat1ng, mmor,liu. 1oow ,tvo� 1,;;r,n11gh, .11r:t ttvir,xi, Thsse w,thdraw,1 symptoms gradually dissipated over th1 ntxl hou,� (1ettro,rn:rpt1;1»ar"m,c rhanges consrstent w,th the effects of drug w1thdr1wat (hypere,citation) were ,ecorded 111 P•t•tnl\ ,1fl@r ,l>f,mi rt,t:�Jtlenge Palients also complained of disturbed 1leep for several weel!s after d1scon!lllul!IQ thm111 with �1911 uo,,91,,, 01 dt0nabinol. OV�IIDOSAGE S1,ns and 1ymptom1 fotto-.,no MILO Manno! (dmnab1Mll 1fftox1uw1 mcluoo ar<!!¥:,1w,o; ,1.,,,"or,1. ht1Qhtened sensory t"areneli. lltered 11me ptrcept,on. reddened con1uncbva. dry mou,1 ,,M t;1cf1yrnd1J 1,,111,'"'"e MOOEfWE mt11uc1tioo mcfude memory impairment. depeoonal1zat1on, ITOld a1ter1t1on. w1n,iy rtten1,r111 .111d ,t>flur,ed twel mobt,ly, and lollowing SEVERE intoxication mclude decreased motor coord1qat1on letharo, ;luutf <illfltl .m,t l"�tural hypOl,ns,on. Apprehen• s1wi patients may m:perience panic re.1ct1ons and seizures m,y ott1;1r 1n fltil1e11ts ""''' 1ix1�liHO )'.�1,ur• d•sor�rs The estimated lethal human dose of mtravenou, dronab1001 ,, 30 molkg (2100 '"@l/0 wo1 s,oni�,;.int CNS symptoms m an1,emet,c studies followed oral dose; of O.� mg/kg (2& rng/lll kOI of M1t1001 M11191a11t: A potentially ierious oral 1noes1ton. d recent ;110010 lie ni;n,gtct Jri!h @ur <l�tontennn1t1on In uncon scious patrents with a s,cure airway. ,nst,11 aet,vatl!d ct1:are.,i1 tlO to t(I) � ,n ldult> 1 to 2 g11<g :n mlants) v\8 a naso�a;tric tube. A saline c:athartic or sorb1tot may be ldUtd to 11,e t,,,t oose ol ,,t,v�ted chercoa1 Patoenls expen,nc• ing depress,ve. haflijcinatory or psychotic reactions s11outd be place� '" a qoiet arn and offered reassurance Bmo• d1azepmes (5 to 10 mg diszepam po) mai b1 used for 1,e.1mtM ol ">'.tm!le ag,tat,on Hypoteft,,on usoally responds to Trendelenburo position and IV fluids. Pressors ;r, rarely r•�IIH•d OOIA8E AND lDl!IINISTRATION A,-,1111 lll111l1tlH: Initially, 2.5 mg Marmot (drm"blOOI) ,hOuld ue •llmm,stmo orally twice daily (b.1.d.). befOfi lunch and supper. for patient, uneble to totmt, th,; 5 moid•t dosage of Manno!. the dosaot can be reduced to 2.5 mg/ day, admmrstered as a single dose m the e,emng r,r ,t �adllme If clin1cally md1cated and m the absence of sign1fic1nl adverse eflect5, the dosage may be gradu,lly ,nere,�ed to , m,x,muni of 20 mg/day Marino!. administered in d1v1ded oral doses. Caution should be exercised in uc11a1mo the dosage of Manno! because of the increased frequency of ciose related adverse e<periences at higher 0011gn (,ee PBECAUTIONS). A1li1111tic: Mannol 1s best administered at a11 m,t,11 dose of 5 mg/m2. ijiven 1 to 3 hours p11or to the admini;trat,on of chemotherapy. then every 2 to� hour, afl,r cherllOtt,er,py ,s oivan. for a total of 4 to 6 doses/day. Should the 5 mglm' dose prove lo be ineflect,we. and in tht ,b1enc, of s1onit1c1nt side e!fects. the dose may be escalated by 2.5 mglm' increments to a m1xrmuA1 ol 15 rn!Ym' pe, dose Cautmn should be exercieed in dose esc1lation. however, 1s the mc,dence of disturbing psyclt llfflc symptom; increases s1gnif1cantly at m1,imum dose (see PRECAUTIONS). SAFETY AND HANDLING Marino! (dronabinol) should Ile packaged in a weHlosed container and stored m a cool environment between 8" and 15°C (46' and 59"F). Protect from fme�og No part•colarhazard to health care workers handling the capsules has been identified. Access to abusable drugs such as Marmol presents an occopat,onal hazard for addiction ,n the health care industry. Routine procedures tor handling controlled substances developed to protect the public may not be adequate to protect health care workers lmpleme!llalmn of more effective accounting procedmes and measures to appropriately restrict access to drugs ot this elm may m1mm1ze the nsk of self-administration by health care providers. HOW SUPPLIED MAAINOL' CAPSULES (dronablnol solution In sesame oil in soft gelatin capsules} 2.5 mg white capsule$ (ldentllied Rl). NOC 0054-2601· 1 1 Bottles of 25 capsules. NOC 0054-2601·21 Bottles of 60 capsules. NOC 0054-2601·25 Bottles of 100 capsules. 5 mg dark brown capsules (Identified Rl). NOC 0054•2602· 1 1 : Bottles of 25 capsules NOC 0054-2602-25: Bottles of 100 capsules. 10 mg orange capsules (Identified RL). NOC 0054-2603-11 : Bottles of 25 capsules. MAAINOL' is a registered trademark of Unimed Pharmaceot,cals, Inc and ,s marketed by Roxane Laboratories Inc. under license from Unimed Pharmaceuticals. Inc Manufactured by Banner Gelatin Products Corporation. Chatsworth CA 9131 t DEA ORDER FORM REQUIRED Caution: federal law prohibits dispensing without orescnp\lon, 40561150 Revised December 1994 124 © RU, 1994.
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©1995 Roxane Laboratones, Inc,
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