Cariban 10 mg/10 mg modified-release hard capsules (doxylamine succinate/pyridoxine hydrochloride): Please refer to the Summary of Product Characteristics (SPC) before prescribing.

Abbreviated Prescribing Information.

Presentation: Modified-release hard capsule. Green capsule, containing two types of modified-release pellets, one type containing Pyridoxine hydrochloride and the other containing Doxylamine succinate. For the full list of excipients, refer to the SPC.

Indications: For the symptomatic treatment of nausea and vomiting during pregnancy in adults who do not respond to conservative management. Limitations of use: The combination doxylamine/pyridoxine has not been studied in case of hyperemesis gravidarum.

Dosage and administration: Oral use. Capsules should be swallowed whole with water, without chewing, and must be taken on an empty stomach as onset of action may be delayed, and absorption reduced when administered with meals. If nauseas are in the morning take 2 capsules at bedtime (Day 1). If this dose controls symptoms the next day, continue taking two capsules daily at bedtime. However, if symptoms persist into the afternoon of Day 2, the patient should continue the usual dose of two capsules at bedtime (Day 2) and on Day 3 take three capsules (one capsule in the morning and two capsules at bedtime). If these three capsules do not adequately control symptoms on Day 3, the patient can take four capsules starting on Day 4 (one capsule in the morning, one capsule mid-afternoon and two capsules at bedtime). The maximum recommended dose is four capsules daily. Hepatic impairment: doxylamine is metabolised by the liver and so the dose should be adjusted depending on the degree of hepatic impairment. Renal impairment: due to the potential for metabolite accumulation, the dose should be reduced depending on the degree of renal impairment. Paediatric population: safety and efficacy in children < 18 years, has not yet been established.

Contraindications: Hypersensitivity to the active substances, to any of the excipients, or to any other ethanolamine derivative antihistamines. Concomitant use with monoamine oxidase (MAO) inhibitors, or with potent inhibitors of CYP450 isoenzymes. Porphyria.

Effects on ability to drive and use machines: Cariban has major influence on the ability to drive and use machines. It may cause somnolence and blurred vision, especially during the first few days of treatment. Therefore patients should avoid engaging in activities requiring complete mental alertness, such as driving or using heavy machinery, until cleared to do so by their healthcare provider.

Warnings and Precautions: The anticholinergic effects of this medicinal product may worsen the following conditions: increased intraocular pressure, narrow angle glaucoma, urinary obstruction, thyroid dysfunction, cardiovascular alterations, hypertension, stenosing peptic ulcer, pyloroduodenal obstruction and bladder-neck obstruction. Care should be taken in patients with asthma or other breathing disorders, such as chronic bronchitis and pulmonary emphysema as it has been demonstrated that antihistamines reduce the volume of bronchial secretions and increase their viscosity, thereby making bronchial expectoration more difficult. This may result in respiratory obstruction, which could worsen these conditions. An increased sensitivity of the skin to sunlight, with photodermatitis, has been observed with some antihistamines; thus, sunbathing should be avoided during treatment. Sedating antihistamines of the ethanolamine class, like doxylamine, could mask the warning signs of damage caused by ototoxic drugs. Care should be taken in epileptic patients as antihistamines have occasionally been associated with paradoxical hyperexcitability reactions, even at therapeutic doses. Due to decreased sweating caused by anticholinergic effects, antihistamines may aggravate symptoms of dehydration and heat stroke. Special precautions should be adopted in patients with long QT syndrome, as several antihistamines may prolong the mentioned QT interval. The suitability of treating patients with hypokalemia or other electrolyte disturbances must be evaluated. Early treatment of symptoms related to morning sickness typically in pregnancy, is recommended to prevent progression to hyperemesis gravidarum. Caution should be taken with patients with hyperemesis gravidarum as this combination has not been studied in these cases. Doxylamine succinate may cause somnolence – refer to Effects on ability to drive and use machines section. Cariban is not recommended if a woman is concurrently using central nervous system (CNS) depressants including alcohol as it may result in severe drowsiness leading to falls or accidents. The risk of abuse and drug dependence of doxylamine is low. The occurrence of signs suggestive of abuse or dependence should be carefully monitored, especially in patients with a history of drug use disorders. Cariban contains pyridoxine hydrochloride, a vitamin B₆ analog, therefore additional levels from diet and vitamin B₆ supplements should be assessed. Antihistamines may suppress the cutaneous histamine response to allergen extracts and should be stopped several days before skin testing. This medicinal product contains sucrose (79.5 mg per capsule). Patients with hereditary intolerance to fructose, glucose or galactose malabsorption, or sucrase – isomaltase insufficiency should not take this medicinal product.

Interactions: No interaction studies have been performed with Cariban. For antihistamines of the ethanolamine class, interactions are known with the following medicinal products: anticholinergic agents (tricyclic antidepressants, MAOI, neuroleptics); sedatives (barbiturates, benzodiazepines, antipsychotic agents, opioid analgesics); antihypertensive drugs with sedative effect on the CNS (especially alpha-methyldopa); alcohol; sodium oxybate as a not recommended combination with doxylamine; ototoxic medications (such as antibacterial aminoglycosides, carboplatin, cisplatin, chloroquine and erythromycin); the concurrent use of antihistamines with other photosensitizing medications (e.g. amiodarone, quinidine, imipramine, doxepin, amitriptyline, griseofulvin, chlorpheniramine, piroxicam, furosemide, captopril). Concomitant use of the following drugs should be avoided: drugs that prolong the QT interval (e.g. antiarrhythmic drugs, certain antibiotics, certain drugs for malaria, certain antihistaminic drugs, certain antilipidemic drugs or certain neuroleptic agents); cytochrome P-450 inhibitors (e.g. azole derivatives or macrolides); drugs that cause electrolyte disturbances such as hypokalemia or hypomagnesemia (e.g. some diuretics). Pyridoxine is known to reduce the effect of levodopa although it does not occur if co-administered with an inhibitor of dopa decarboxylase. A reduction in plasma levels of some antiepileptics such as phenobarbital and phenytoin has been described with pyridoxine. Some medications (such as hydroxyzine, isoniazid or penicillamine) may interfere with pyridoxine and may increase requirements for vitamin B₆. The anticholinergic effects of doxylamine could lead to false negatives in dermal hypersensitivity tests with antigen extracts. It is recommended to discontinue the treatment several days before starting the test.

Fertility, pregnancy and lactation: Cariban is intended for use in pregnant women. Epidemiological studies and meta-analyses indicates no malformative toxicity of doxylamine succinate and pyridoxine hydrochloride. Due to the anticholinergic and sedative properties of doxylamine succinate, caution should be taken with the newborn in case of mother’s treatment until delivery. Physico-chemical data suggest excretion of doxylamine succinate in human breast milk and a risk to the suckling child cannot be excluded. Cariban is not recommended during lactation. A study of doxylamine in rats does not produce adverse effects on fertility. For further information, refer to SPC. No human data are available.

Undesirable effects: Adverse reactions associated with the use of the combination of doxylamine/pyridoxine are comparable to those occurring with the sedating antihistamines as the sole active ingredient. Common (≥1/100 to <1/10): somnolence, dry mouth, constipation, vision blurred, urinary retention and increased bronchial secretion. Uncommon (≥1/1,000 and <1/100): confusional state, nausea, vomiting, diarrhoea, diplopia, glaucoma, asthenia, oedema peripheral, orthostatic hypotension, tinnitus, rash and photosensitivity reactions. Rare (≥1/10,000 to <1/1,000): tremor, convulsion, agitation and haemolytic anaemia. Not known (frequency cannot be estimated from the available data): vertigo, tachycardia and dyspnea.

Overdose: Refer to SPC.

Legal Category: This product is subject to medical prescription.

MIMS Ireland Price: €12.59 per 24 capsule pack.

MA Number: PA 1776/002/001.

Full prescribing information available from: Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 5UA, United Kingdom.

Date of Preparation: April 2024.